Rotator Cuff Tears

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Rotator cuff tears
Article in Nature Reviews Disease Primers · February 2024

DOI: 10.1038/s41572-024-00492-3
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Rotator cuff tears

Asheesh Bedi1,2, Julie Bishop3, Jay Keener4, Drew A. Lansdown5, Ofer Levy6, Peter MacDonald7, Nicola Maffulli 8
,
Joo Han Oh9, Vani J. Sabesan10, Joaquin Sanchez-Sotelo11, Riley J. Williams III12 & Brian T. Feeley 5
Abstract Sections
Rotator cuff tears are the most common upper extremity condition seen Introduction
by primary care and orthopaedic surgeons, with a spectrum ranging Epidemiology

from tendinopathy to full-thickness tears with arthritic change. Some Mechanisms/pathophysiology
tears are traumatic, but most rotator cuff problems are degenerative.
Diagnosis, screening and
Not all tears are symptomatic and not all progress, and many patients prevention
in whom tears become more extensive do not experience symptom
Management
worsening. Hence, a standard algorithm for managing patients is
Quality of life
challenging. The pathophysiology of rotator cuff tears is complex
and encompasses an interplay between the tendon, bone and muscle. Outlook
Rotator cuff tears begin as degenerative changes within the tendon,

with matrix disorganization and inflammatory changes. Subsequently,
tears progress to partial-thickness and then full-thickness tears. Muscle
quality, as evidenced by the overall size of the muscle and intramuscular
fatty infiltration, also influences symptoms, tear progression and the
outcomes of surgery. Treatment depends primarily on symptoms, with
non-operative management sufficient for most patients with rotator
cuff problems. Modern arthroscopic repair techniques have improved
recovery, but outcomes are still limited by a lack of understanding of
how to improve tendon to bone healing in many patients.
1
Department of Orthopedic Surgery, University of Chicago, Chicago, IL, USA. 2NorthShore Health System,
Chicago, IL, USA. 3Department of Orthopedic Surgery, The Ohio State Wexner Medical Center, Columbus, OH,
USA. 4Department of Orthopedic Surgery, Washington University, St. Louis, MO, USA. 5Department of Orthopedic
Surgery, University of California San Francisco, San Francisco, CA, USA. 6Reading Shoulder Unit, Berkshire
Independent Hospital, Reading, UK. 7Department of Surgery, Max Rady College of Medicine, Winnipeg, Manitoba,
Canada. 8Department of Trauma and Orthopaedic Surgery, Faculty of Medicine and Psychology, University of
Rome Sapienza, Rome, Italy. 9Department of Orthopedic Surgery, Seoul National University College of Medicine,
Seoul National University Bundang Hospital, Seoul, Korea. 10HCA Florida JFK Orthopaedic Surgery Residency
Program, Atlantis Orthopedics, Atlantis, FL, USA. 11Department of Orthopedic Surgery, Mayo Clinic, Rochester,
MN, USA. 12Department of Orthopedic Surgery, Hospital for Special Surgery, New York, NY, USA.
e-mail: Brian.feeley@ucsf.edu
Nature Reviews Disease Primers | (2024) 10:8 1

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Introduction Epidemiology
The rotator cuff is a group of muscles and tendons that maintains the Prevalence
shoulder in place and provides dynamic motion and stability to Patients can develop shoulder pain at any point along the spectrum
the joint. It is composed of four separate muscles, namely the supraspi- of rotator cuff tears. Most patients with a rotator cuff tear do not have
natus, infraspinatus, subscapularis and teres minor. The tendons from symptoms of pain or weakness and do not seek medical care. Hence,
these four muscles coalesce at their attachments on the humeral head the exact prevalence of rotator cuff disease is unknown. Although the
(Fig. 1). The glenohumeral joint has the greatest range of motion of incidence of symptomatic rotator cuff disease is probably steady, rota-
any joint in the human body, and inherently relies upon the rotator tor cuff repair surgery is more common than 20 years ago, probably
cuff to provide dynamic stabilization as well as function to position due to the increased use of arthroscopic techniques and transition
the arm and hand. to outpatient surgery. One study showed an annual increase in rota-
Rotator cuff tears are the most common upper extremity con- tor cuff surgery of 1.6% per year in the USA between 2007 and 2016
dition seen by primary care physicians, physiatrists and orthopae- (165 repairs per 100,000 person-years10). In the absence of pain, indi-
dic surgeons1. Rotator cuff injuries present as a spectrum of disease viduals with rotator cuff tears have been shown to maintain nearly nor-
ranging from tendinopathy and partial-thickness tears, extending to mal shoulder function11. Population screening studies using shoulder
full-thickness tears with progressive cartilage degeneration (cuff tear ultrasonography have better defined the prevalence of rotator cuff
arthropathy)2 (Box 1 and Fig. 2). Symptoms of rotator cuff injuries are tear12. A cross-sectional study involving 1,000 women in the UK demon-
broad and can range from minimal symptoms including difficulty strated that 22.2% had a full-thickness rotator cuff tear. Advancing age
sleeping and pain during overhead reaching to loss of active and passive and dominant shoulder involvement were positively correlated with
motion with progressive shoulder girdle weakness and dysfunction. the presence of a tear. Similarly, two different observational studies
Although some tears are traumatic, most rotator cuff problems in Asian populations showed a prevalence of full-thickness cuff tears
are degenerative in nature due, in part, to age-related changes to the of 20.7% (1,366 individuals) and 22.1% (664 individuals), with higher
tendon structure. The leading hypothesis is that tears progress from prevalence in individuals ≥57 years of age than in younger individuals
tendinopathic changes in a watershed area that lacks blood supply and in men than in women13,14.
in the supraspinatus to partial-thickness tears and eventually full-
thickness tears3, which are accompanied by progressive muscle and Risk factors
tendon degeneration. Confounding the natural history is that not all Age. The overwhelming clinical evidence suggests that the primary
tears progress and/or worsen, and in many patients who present with a risk factor for the development of rotator cuff degeneration is age4,5,15,16.
progressive increase in the tear size, symptoms do not worsen, making Multiple clinical studies have shown that patients with a painful rotator
a standard algorithm for treatment challenging4,5. cuff tear often have an asymptomatic degenerative tear in the opposite
The pathophysiology of rotator cuff tears is complex, as it involves shoulder5,11,17,18. One study performed bilateral shoulder ultrasonog-
the interplay between the tendon, bone and muscle. A key to under- raphy on patients presenting with unilateral shoulder pain, and dem-
standing rotator cuff pathology and tearing is delineating the role of onstrated a strong association between cuff disease and ageing19. The
tendon and muscle degeneration. Increasing evidence suggests that presence of a full-thickness tear in the painful shoulder was associated
the mTOR pathway might have an important role in the regulation of with a 21% risk of a partial-thickness tear and 36% risk of a full-thickness
tendon degeneration over time6. Muscle quality, as evidenced by the tear in the contralateral shoulder. The average age of those with an
overall size of the muscle, as well as intramuscular fat deposition (fatty intact cuff, a unilateral cuff tear and bilateral partial-thickness or
infiltration) also influences shoulder strength, tear progression and full-thickness cuff tears demonstrated a nearly perfect 10-year distri-
the outcome of surgery7. Studies also highlight the role of fibroadipo- bution (48.7, 58.7 and 67.8 years of age, respectively)17. Patients with a
progenitor cells (FAPs) (muscle-resident multipotent mesenchymal full-thickness cuff tear on the symptomatic side had a 50% chance of
stem cells (MSCs)) as a central mediator of muscle degeneration8,9. having a concomitant cuff tear on the asymptomatic side at ≥66 years
The management of rotator cuff tears is generally based on of age. One study involving pooled data from 30 separate studies and
symptoms. Indeed, most patients with rotator cuff tears diagnosed >6,000 shoulders demonstrated a strong correlation between the pres-
on advanced imaging (for example, MRI or ultrasonography) do not ence of a tear and increasing age stratified by decade, with a prevalence
require surgery. Observation, physical therapy and corticosteroid of 9.7% in those <20 years of age compared with a prevalence of 62% in
injections, as well as surgical repair and reconstruction of the rotator those >80 years of age20.
cuff, all play a role in patient recovery, which depends on many patient-
specific factors such as age, activity level and hand dominance, and Genetics. Genetics may play a role in the development of rotator cuff
intrinsic factors of the rotator cuff. disease (Box 2). One study demonstrated a familial association of
Of note, the terminology of rotator cuff disease in the literature rotator cuff disease, noting that siblings were twice as likely as spouses
varies: a rotator cuff problem is described as a tendinopathy, a tear, to develop a full-thickness cuff tear, regardless of symptoms, and
an injury or rotator cuff disease. Thus, the nomenclature leads to more than four times as likely to develop a painful full-thickness tear
confusion for the patient and the provider. compared with the general population21,22. Additionally, progression
In this Primer, we present the current knowledge of the basic and of tear size at 5-year follow-up was greater in siblings than controls23.
clinical science of rotator cuff disease, highlighting the clinical pres- Studies have shown an association between variants in genes related to
entation, natural history, risk factors and current treatment options. cellular apoptosis on chromosome 6 and chromosome 17 and rotator
Furthermore, we provide an evidence-based treatment algorithm and cuff disease24. Indeed, genome-wide association studies have shown
consolidate the unmet needs in the field as well as outline the barriers variants in multiple candidate genes using large population-based
necessary to overcome the modest improvements in outcomes of genetic databases25,26. RNA sequencing of the UK Biobank showed an
surgery over the past 20 years. increased expression of STK24 and a decreased expression of SAT1

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Anterior view Posterior view

Acromion Supraspinatus Acromion
Subacromial bursa
Supraspinatus
attachment
Humeral
head
Humeral head
Long head of
biceps tendon
Subscapularis
Teres minor
Infraspinatus
Fig. 1 | Structural anatomy of the rotator cuff when viewed from the anterior stabilize the shoulder against posterior subluxation and is the primary muscle
and posterior aspects. The tendons of the teres minor, infraspinatus and responsible for external rotation of the shoulder. The teres minor lies below the
supraspinatus are continuous on the humeral head. The supraspinatus muscle infraspinatus, with a common origin along the medial border of the scapula.
lies on the superior portion of the scapula and inserts on the anterior aspect It provides up to 45% of the external rotation force. The subscapularis lies on the
of the greater tuberosity of the humeral head. The primary function of the anterior portion of the scapula and attaches to the lesser tuberosity. Its primary
supraspinatus is forward and lateral elevation of the shoulder, and it assists in function is internal rotation of the shoulder and it also acts as a force couple
rotation of the arm. It is the most commonly torn rotator cuff tendon, involved (along with the infraspinatus) against the deltoid, keeping the shoulder stabilized
in 70–85% of rotator cuff tears13. The infraspinatus lies below the scapular spine within the joint against the pull of the deltoid302. The long head of the biceps
and attaches posterior to the supraspinatus on the rotator cuff. It functions to tendon runs between the supraspinatus and subscapularis in the rotator interval.
and UBE2D3 following rotator cuff tear27. These genes have suspected diabetes34. Studies have demonstrated that diabetes mellitus is a definite
roles in inflammation and angiogenesis. Additional genes identified risk factor for impaired healing after rotator cuff surgery, and those
have known roles in mediating cytokine expression, neutrophil and patients with a lower HbA1c (<7%) in the postoperative period have
macrophage activation, and response to oxidative stress28; however, lower retear rates than patients with higher HbA1c (>7%), suggesting
none is specific to the tendon injury and remodelling. Currently, the an important role of diabetes mellitus in controlling tendon to bone
exact role of genetics in the development of degenerative rotator cuff healing35,36. Evidence also shows that there is an association between
disease is unknown. Nevertheless, an increasing body of evidence sup- oestrogen deficiency in women and testosterone deficiency in men and
ports a genetic predisposition in some patients. In addition, sex and outcomes following surgery for a rotator cuff tear37. Similarly, in an insur-
ethnicity are not consistently identified as risk factors for developing ance database study, women with oestrogen deficiency were 48% more
degenerative rotator cuff disease. likely and men with testosterone deficiency were 89% more likely than
age-matched controls to undergo rotator cuff repair surgery38. The exact
Comorbidities. Several disease conditions have been postulated to mechanism of hormone deficiencies and their contribution to rotator
have a role in the development and progression of rotator cuff disease, cuff tears, at the cellular level, have not been elucidated at this point.
and subsequently, may influence healing rates following surgical repair.
These conditions include type 2 diabetes mellitus, hyperlipidaemia, sex Physical activity and occupation. The role of physical activity in
hormone deficiency, obesity, smoking, hypertension, gout, connective the development of rotator cuff disease is debated. Studies in rats
tissue diseases and depression23,29–33. Diabetes mellitus promotes the have shown that excessive physical activity promotes supraspinatus
development of tendinopathy in several areas, including the rotator tendinopathy. The changes induced in the tendon include increased
cuff and Achilles tendon, perhaps owing to altered neural, vascular and tendon hypertrophy and decreased elasticity and were associated
immune responses to tissue remodelling3. Samples of torn rotator cuff with a combination of intrinsic and extrinsic factors (compression
tendons from patients with diabetes mellitus show higher expression from the coracoacromial arch)39,40. By contrast, one study failed to
of matrix metalloproteinases, such as MMP2, and higher expression of show an association between the level of overhead physical activity or
inflammatory proteins (IL-6) than samples from individuals without occupational demands with tear progression in a cohort of patients with

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have been linked to rotator cuff disease, no studies have examined

Box 1 the effects of these conditions on the natural history or progression
of rotator cuff disease. The role of scapular morphology, specifically
the acromion, in the development of and the progression of degenera-
Classification of rotator cuff tive rotator cuff tears is debated. For example, in one study, the critical
shoulder angle of patients with an asymptomatic rotator cuff tear was
tears larger than in control patients with normal rotator cuffs but was not
associated with tear size or the risk of tear enlargement (median time
Tears are classified based on their size (partial or complete), and to enlargement of 3.3 years)51. Other studies, including a meta-analysis,
several classification systems are used. Most commonly, partial demonstrated considerable variability in the relationship between criti-
tears are classified based on the amount of tearing off the footprint cal shoulder angle and the presence of rotator cuff tears, suggesting
(Ellman classification) as seen on MRI. Full thickness tears are that it may only be a factor in some patients52.
usually classified with the Codman classification based on tear size The typical site of initiation of a rotator cuff tear is between
in the anterior–posterior dimension. Although these classifications 13 mm and 17 mm posterior to the biceps tendon within the rotator
lack high reproducibility, the Codman classification is predictive crescent16,53. The rotator crescent is a relatively hypovascular area of
of outcome after rotator cuff repair, and helps guide treatment the posterior cuff that is protected to some degree biomechanically
decisions. The Goutallier classification is utilized to determine the by the thick rotator cable, which spans from the anterior edge of the
degree of fatty infiltration within the rotator cuff, and is assessed supraspinatus to the inferior infraspinatus54–56. Approximately 30% of
on sagittal views on MRI. full-thickness tears, regardless of tear size, involve the anterior cable
tissue adjacent to the biceps tendon, and only 3% of small full-thickness
Partial-thickness tears — Ellman classification301 tears (≤10 mm) involve this area53,57. Longitudinal studies have shown
•• Grade 1: <3 mm (<25% thickness) that tear enlargement within the rotator crescent is common in the
•• Grade 2: 3–6 mm (25–50% thickness) anterior and posterior directions4. Rotator cuff tear location mapping
•• Grade 3: >6 mm (>50% thickness) has shown that anterior cable disruption is strongly associated with
•• Location: A, articular sided; B, bursal sided; C, intratendinous supraspinatus muscle degeneration16,58.
Pain is an important clinical indicator of tear size progression
Full-thickness tears — Codman classification (tear size over time with the tear width and amount of retraction from the bone
in anterior to posterior direction)302 increasing. Much of the research examining tear progression has been
•• Small: 0–1 cm performed in asymptomatic shoulders by identifying painless tears in
•• Medium: 1–3 cm patients presenting with a painful cuff tear in the opposite shoulder.
•• Large: 3–5 cm Clinically, most patients in whom the tear progressed had an increased
•• Massive: >5 cm risk of developing pain59. In a large study of 224 shoulders in patients
with asymptomatic tears in one shoulder and a contralateral painful
Fatty infiltration — Goutallier classification160 rotator cuff tear, tear progression was found in 49% of asymptomatic
•• Normal: score 0 shoulders by ultrasonography, with a median time to enlargement of
•• Fatty streaks: score 1 2.8 years5. In this study, the risk of tear enlargement for full-thickness
•• More muscle than fat: score 2 tears was significantly greater than for partial-thickness tears and
•• Equal fat and muscle: score 3 control shoulders. Overall, 46% of originally asymptomatic shoulders
•• More fat than muscle: score 4 developed pain at a median of 2.6 years. A subsequent study involv-
ing 227 shoulders in patients aged 65 years or younger demonstrated
continued tear progression over an average follow up of 7.1 years43.
asymptomatic tears41. For degenerative tears, evidence shows that activ- Overall, 60% of tears enlarged during the 7-year study period. The risks
ity tear development is linked to hand dominance, with higher likelihood of enlargement of a full-thickness tear at 2 years, 5 years and 8 years
of a symptomatic tear in the dominant shoulder than the non-dominant were 26%, 58% and 80%, respectively. Approximately 57% of the cohort
shoulder13,41–43. Occupational demands might play a part in rotator cuff developed pain, which was strongly linked to tear enlargement.
tear development; for example, studies have identified several occu- The presence and progression of degeneration of the supraspinatus
pational exposure risk factors, such as repetitive arm elevation, heavy and infraspinatus muscles were linked to absolute tear size and tear
lifting and use of vibrating tools, that are associated with rotator cuff enlargement during follow-up43.
tears44–48. However, the exact duration and type of exposure that con- Clinical evidence strongly suggests that symptomatic degenera-
stitute a risk is unknown. A study in a population of >250,000 individu- tive full-thickness rotator cuff tears do not heal, and most tears are at
als (UK Biobank) showed a correlation between self-reported manual risk of slow progression over time. Tear progression can be defined
labour and the need for rotator cuff surgery compared with controls, as tear enlargement or progression of muscle degeneration — both of
particularly when the occupational exposure lasted >10 years49. which have implications on healing potential following surgical repair.
Multiple studies have demonstrated that painful tears will enlarge in
Natural history size, especially over a period of 18 months or more, but the amount
Although, the greatest risk factor for rotator cuff tear development is of tear enlargement is relatively low50,60. For example, in 49 patients
age, time is the greatest risk factor for tear progression. The risk of tear with a symptomatic full-thickness rotator cuff tear, the average tear
enlargement is greater in full-thickness tears than partial-thickness size increase was <1 cm, and progression of muscle degeneration was
tears5,43,50. Although smoking, obesity, diabetes and hyperlipidaemia seen in <50% of patients59.

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Rotator cuff muscle degeneration refers to the development present with new-onset pain, from a purely biological viewpoint, might
of muscle atrophy and fatty cell infiltration into the muscle. Rotator have well-established histopathological changes. Why a biologically
cuff muscle degeneration is almost exclusive to full-thickness rotator cuff long-standing condition suddenly manifests itself in an acute fashion
tears16,57. In one study, tears that enlarged had more than twice the risk is still unclear.
of progression of muscle degeneration than stable tears61. Additionally, The present scientific evidence suggests that the initial lesion
when tear progression led to disruption of the anterior cable or when of tendinopathy is a failed healing response to microtrauma, and the
the extent of tear enlargement was big, the risk of progression of muscle role of inflammation in these conditions has been re-evaluated and
degeneration increased over time after adjusting for covariates16,61. is thought to be an important contributor71,72 (Fig. 3). In the devel-
opment of tendinopathy of the rotator cuff, an increase in inflam-
Mechanisms/pathophysiology matory cells and production of pro-inflammatory cytokines from
Rotator cuff tears represent a spectrum of disease, from impingement, tenocytes are thought to have a role3,73. Animal models of tendino
tendinopathy, to partial-thickness tears and to full-thickness tears of pathy show increased numbers of macrophages and mast cells within
varying sizes (Fig. 2). Impingement (originally named after the idea the injured tendon74. In response to altered mechanical load or
that the acromion impinges on the rotator cuff62) occurs when the tissue injury, tenocytes and immune cells within the tendon release
bursa above the rotator cuff is inflamed as a consequence of altered pro-inflammatory cytokines, including TNF, IL-6 and IL-1β. IL-17A has
kinematics of the shoulder girdle. When the larger muscles (deltoid) been found to be upregulated in patients with a rotator cuff tear75.
over-compensate due to rotator cuff dysfunction, the rotator cuff IL-17A was expressed in various inflammatory cells within rotator cuff
cannot function as an effective force couple, resulting in the humeral tendon, and tenocytes that were treated with IL-17A had increased
head elevating rather than depressing during shoulder motion63,64. production of pro-inflammatory cytokines, and increased expres-
This altered movement pattern increases inflammation within the sion of apoptosis-related factors75. The role of IL-17A is notable given
rotator cuff bursa above the tendon, leading to pain with motion and the availability of anti-IL-17A monoclonal antibodies (secukinumab
overhead activity, and pain during sleep. Although imaging findings and ixekizumab) that have been evaluated for their role in treating
are normal in patients with mild impingement, increased fluid signal tendinopathy3.
on ultrasonography or MRI above the rotator cuff is a key indication of In most patients, partial-thickness tears and full-thickness tears
active impingement. Studies have suggested that the bursa is a source are hypothesized to be the result of the tendinopathy process over
of active healing of the cuff, by stimulating inflammatory cells and fac- a period of many years. Histologically, tendinopathy demonstrates
tors that promote healing65–67. The bursal cells display mesenchymal altered collagen organization with increased inflammatory tissue with
markers of stemness, including CD73 and CD90, and, in experimental decreased vascularity, which, for as-yet unidentified reasons, may not
models of bursa–tendon crosstalk, the bursa has upregulated markers necessarily cause symptoms even as tendinopathy progresses into
of extracellular matrix production (TGFβ), immune cell signalling and partial-thickness and full-thickness tears. The severity of tear as well
vascular signalling including PDGFRβ68. as the extent of tendinopathy do not correlate with patient symptoms,
The exact mechanisms of how rotator cuff injury progresses from which highlights the complex relationship between degeneration,
tendinopathy to partial-thickness tears and to full-thickness tears is pain development and pain perception at the central nervous system
yet to be fully understood. In addition, the inconsistent terminology level. An upregulation of the glutamatergic system has been observed
commonly used even among orthopaedic surgeons can be confus- in patients with rotator cuff tendinopathy, with localization of glu-
ing and misleading to patients and providers alike69,70. Patients who tamate to tenocytes with glutamate receptors on macrophages76.
Rotator cuff spectrum of disease

Impingement Partial-thickness tear Small full-thickness tear Massive full-thickness tear
Symptoms Symptoms
• Overhead pain, night pain, minimal weakness • Pain, weakness
Examination Examination
• Range of motion and strength intact • Global rotator cuff weakness and
• Impingement signs and painful arc test external rotation lag sign
Pathophysiology Pathophysiology
• Tendinopathy and/or degeneration • Muscle atrophy, fatty infiltration
Fig. 2 | Representative pathology and functional differences in rotator cuff findings on clinical examination. Patients with larger and massive tears will have
pathology. Impingement, partial-thickness and small full-thickness tears present lost their force couple and have difficulty elevating their arm, and are more likely
with similar symptoms, with pain on overhead activity, pain at night and variable to have a positive external rotation lag test than patients with small tears.

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tendons, possibly secondary to inflammation and abnormal oxidative

Box 2 stresses80. Anti-oxidative and anti-inflammatory therapies that mitigate
or suppress these pathways might have therapeutic benefit by altering
the natural history of tendinopathy in these settings.
Risk factors for rotator cuff
Oxidative stress. Oxidative stress activates signalling pathways that
disease and progression generate reactive oxygen species, which induce inflammation and in
excessive quantities, damage cells, lipids, proteins and even DNA81,82.
Non-modifiable risk factors Clinical studies have shown increased levels of serum hydroperox-
•• Age ides in tendinopathic tendon tissue and increased concentrations
•• History of contralateral rotator cuff tear of inflammatory proteins in the synovium and tendon in rotator cuff
•• Genetics tears28. In animal models, increased mechanical loading and tendon
•• Familial association overuse increased the plasma total oxidant status and circulating
•• Single nucleotide variants (apoptosis-related genes) pro-inflammatory cytokines79. Multiple pathways are likely to be
•• Genome-wide association studies (STK24 upregulation; SAT1 involved, and activation of the mTOR pathway6, resulting in tissue
and UBED3 downregulation) metaplasia and impaired tenogenesis of tendon-derived stem cells83,
•• Hand dominance may have a major role in tendon degeneration and impaired tendon
•• Scapular morphology healing. Interestingly, mTOR is also a central regulator of muscle atro-
phy; hence, targeting this pathway may serve a dual role in future
Modifiable risk factors treatment strategies84.
•• Diabetes mellitus Obesity, diabetes mellitus or hypercholesterolaemia further pre-
•• Smoking dispose to a pro-inflammatory environment and increase the risk for
•• Hyperlipidaemia degenerative tendinopathy. In individuals with comorbidities, reactive
•• BMI oxidative species are increased in these settings, triggering tenocyte
•• Hypertension apoptosis, fibrosis and tissue metaplasia via mTOR, nicotinamide dinu-
•• Work factors cleotide phosphate oxidase (NOX) and AKT/FOXO1 pathways82,85. Drugs
•• High dynamic strength such as fluoroquinolones or local anaesthetics such as bupivacaine also
•• Whole-body vibration predispose to tendinopathy, probably by altering mitochondrial mem-
•• Heavy lifting brane permeability and/or generating reactive oxygen species in cells,
thereby inducing oxidative stress and a catabolic, pro-inflammatory
Risk factors for tear progression response86,87.
•• Increasing age Accordingly, anti-oxidants that reduce the production of reactive
•• Increasing time from diagnosis oxidative species or drugs such as rapamycin, which inhibit down-
•• Increasing tear size (full thickness > partial thickness) stream pathways (for example, mTOR), are being actively investi-
•• Location of tear (through rotator cuff cable) gated for managing symptomatic tendinopathy6. Studies examining
natural anti-oxidants such as curcumin, eugenol and flavonoids, are
ongoing80,88. Well-designed clinical studies assessing the efficacy of
Further, other nociceptive mediators such as mGLuR2 and GluK1 these therapies in symptomatic patients are warranted.
are also upregulated in patients with tendinopathy76. Interestingly,
tenocytes exposed to glutamate in vitro show decreased cell viability Muscle quality
and decreased collagen gene expression77, providing a possible link Muscle quality, defined by the development of muscle atrophy and
between pain and tendon degeneration. fatty infiltration, has been implicated as a key factor affecting the
outcomes of rotator cuff injury and repair (Fig. 3). Muscle atrophy,
Tendon degeneration a likely consequence of mechanical unloading of the tendon and fatty
The cellular and molecular pathophysiology of degenerative tendino infiltration, which seems to be chronic resulting from alterations in
pathy is highly complex and is only partially understood. A myriad innervation, affects rotator cuff treatment outcomes. Patients with
of predisposing factors, including patient-specific factors such as greater muscle atrophy and increased fatty infiltration are at higher
metabolic disorders (that is, hypercholesterolaemia, hyperglycae- risk of retear after surgery, and worse clinical outcomes than those
mia), mechanical overuse and repetitive microtrauma, drug exposure with less muscle atrophy, even with a technically successful repair7,89.
and ischaemia contribute to profound structural changes within the
tendon3. Both animal-based and clinical studies have demonstrated that Muscle atrophy. Atrophy is defined as the loss of muscle mass, with
activation of secondary inflammatory pathways and oxidative stress in a physiological shift from protein synthesis to protein degradation90.
tendon tissue promote tenocyte apoptosis, fibrosis and disorganization Atrophy is an independent factor that predicts outcomes after rotator
of the extracellular matrix and, in some cases, heterotopic ossification cuff repair. The degree of atrophy is used in combination with fatty
(a condition in which bone tissue develops in soft tissue)28,78,79. Impor- infiltration and the amount of tendon retraction to gauge the ‘repair-
tantly, chronic tears are the result of consistent tendon abnormalities in ability’ of a rotator cuff tear. Full-thickness rotator cuff tears result in
the tendon tissue that has been degenerated over a long time. Studies alterations in mechanical load to the muscle–tendon unit, which nega-
have demonstrated tissue metaplasia, tenocyte apoptosis and reduced tively affect key protein activation, including AKT and mTOR, and alter
regenerative properties of tendon-derived stem cells in tendinopathic the expression of atrophy-related genes (atrogenes), such as MuRF1

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and ATROGIN1 (refs. 91–93). These findings have highlighted the shift gain-of-function and loss-of-function studies have shown little dif-
from protein synthesis to autophagy, as well as increased proteasomal ference in muscle size in a mouse model of full thickness rotator cuff
activity and atrophy of individual muscle fibres84,94. The central regu- tears90. Relatively few studies have evaluated the role of the primary
lators of atrophy are yet to be defined. NF-κB is a transcription factor muscle stem cell, the satellite cell, in the maintenance of muscle size.
thought to be a key mediator of muscle atrophy in several pathologi- In animal models of full-thickness rotator cuff tears, the number of
cal states, including cancer cachexia and ageing95. However, the role satellite cells remained constant96, suggesting that the presence
of NF-κB in rotator cuff tear-induced atrophy seems to be minimal, as of a tear does not cause depletion of this important muscle stem cell.
a
Tendinopathy Muscle quality
• Altered mechanical load • Altered load, denervation
• Altered vascularity • Atrophy
• Key proteins: mTOR, AKT, MMPs • FOXO1, AKT, mTOR
• Fatty infiltration
• FAP stem cells
• PPARγ, CREBP, DLK1
Tendon–bone healing
• Biomechanical
fixation
• PRP, MSC
augmentation
• Growth factors:
VEGF, TGFβ, IGF
b Subacromial spur Pectoralis muscle

length
Subacromial
Acromion shape Scapular muscle
impingement
performance
Extrinsic mechanisms
• Originates external Anatomical and
Acromioclavicular spur
to tendon biomechanical Thoracic spine posture
• Compression or shear and mobility
Internal
Scapular kinematics
impingement
Glenohumeral capsule
length and extensibility
Humeral kinematics
Rotator cuff muscle
Rotator cuff
performance
tendinopathy
Tendon vascularity
Tendon biology PG, GAG and collagen content

Intrinsic mechanisms
• Originates within
tendon
• Degenerative Tendon mechanical
Tendon, strain and stiffness
processes properties
• Potentially associated
with ageing
Tendon morphology Thickness, irregularity
Genetic Polymorphism of collagen,

predisposition other factors
Fig. 3 | Muscle and tendon biology of the rotator cuff. a, Tendinopathy is Extrinsic factors, including anatomical changes such as acromial bone spurs
caused by a variety of factors including overuse, mechanical load alterations and and degeneration of the acromioclavicular joint, cause impingement on the
changes in vascularity. Muscle degeneration, which is due to muscle atrophy rotator cuff tendon. Alterations in shoulder kinematics similarly cause extrinsic
and fatty infiltration, is typically seen in the setting of a large rotator cuff tear. load alterations as well as changes in muscle forces across the shoulder joint.
Tendon–bone healing is primarily influenced by the biomechanical repair Intrinsic degeneration is due, in part, to alterations in collagen structure
strategy, and treatments such as platelet-rich plasma (PRP) and mesenchymal and orientation, changes in vascularity, and probably genetic factors that
stem cell (MSC) delivery have been shown to improve retear rates, but not to predispose some patients towards tendinopathy. These changes result in
affect clinical outcomes. b, The pathogenesis of rotator cuff is complicated, increased tendon stiffness and loss of the intrinsic structure of the tendon. FAP,
with both extrinsic and intrinsic factors contributing to tendon degeneration. fibroadipoprogenitor.

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Similarly, in human studies, satellite cell numbers are not diminished, phases129,130. These cytokines induce paracrine and autocrine responses
but their ability to contribute to muscle size and regeneration may be that affect fibroblast migration, angiogenesis, collagen production
limited in the setting of aged rotator cuff tissue97–101. and matrix metalloproteinase activity131. Variations in both the quan-
tity and temporal expression of these cytokines markedly affect the
Fatty infiltration. Fatty infiltration (that is, infiltration of fat from the healing response at the enthesis, including the potential to shift from
surrounding tissue102) has emerged as an important biological concept fibrosis and scar formation to tissue regeneration. Accordingly, there
involved in muscle degeneration across many conditions, including is a tremendous focus on augmenting tendon–bone healing through
ageing, low back pain and muscular dystrophy. The presence of fatty modulation of these growth factors or through a paracrine effect of
infiltration worsens the quality of muscle, as the amount of tissue secretomes associated with local stem cell recruitment or delivery131–133.
that can develop force decreases with a concomitant alteration in
the biomechanical properties of the tissue103. Several animal studies Diagnosis, screening and prevention
and human studies have demonstrated the importance of FAPs in Clinical presentation
the development of fatty infiltration9. These cells have a central role Patients with a symptomatic rotator cuff tear typically present at
in the regulation of muscle degeneration; for example, in muscular ~50–70 years of age, with pain at night that keeps them from sleeping,
dystrophy, amyotrophic lateral sclerosis and ageing104–111. In animal pain with overhead activity such has reaching a high shelf, or a subjec-
models, FAPs have been shown to proliferate at the time of rotator tive feeling of shoulder girdle weakness. Despite a clear pathophysi-
cuff injury and directly contribute to the development of fatty infil- ological progression from tendinopathy to partial-thickness tears to
tration through expression of white fat-associated genes including full-thickness tears, symptom severity does not necessarily correlate
PPARG, CREBP and other fat-related genes84,96,112. Fatty infiltration can with histopathological severity (Fig. 4).
be decreased through inhibition signalling molecules, such as TGFβ,
retinoic acid and PPARγ, which probably work through modulating Diagnosis
the response of FAPs to injury113–116. In human studies, FAPs prolifer- The diagnosis of a rotator cuff tear is based on the location of pain
ate at the time of rotator cuff injury, and increase in number as tear (typically along the lateral shoulder), timing of pain (nocturnal
size progresses8 and express several fat-related and fibrosis-related pain and pain with overhead activities) and key physical examination
genes117–119. Non-biased transcriptomic studies have shown that FAPs findings. However, the location and type of pain described by patients
isolated from partial-thickness tears are less likely to express mark- are often non-specific and only beneficial to a certain extent. Under-
ers of adipogenesis and fibrosis than FAPs from full-thickness tears. standing the symptoms of rotator cuff pathology in comparison with
Adipogenic commitment is driven by downregulation of DLK1, which other common shoulder ailments, especially frozen shoulder and gle-
is seen in FAPs from patients with full-thickness tears120. Importantly, nohumeral arthritis, is important. The differential diagnosis of rotator
FAPs also seem to have pro-regenerative capabilities in vitro when cuff tears is broad and should include degenerative conditions of the
stimulated with pharmacological agents, which may be utilized to shoulder girdle and the cervical spine (Table 1). Physical examination
improve muscle quality at the time of and after rotator cuff repair121–124. of the patients suspected to have rotator cuff pathology should focus
on the integrity and functioning of the rotator cuff and periscapular
Tendon healing after repair muscles. Despite advances in imaging techniques, history and physical
Tendon–bone healing, a highly complex process, is crucial to the suc- examination remain the primary diagnostic tools and determinants
cess of rotator cuff repair; yet, the mechanism underlying this process of management.
remains a critical unmet need in this field. The native enthesis is a highly
organized structure with remarkable architecture designed to transmit Physical examination. Physical examination must begin by expos-
loads from muscle through unmineralized and mineralized fibrocarti- ing both shoulder girdles to assess their symmetry. Muscle atrophy,
lage to bone125,126. Re-establishment of the rotator cuff tendon to bone in the infraspinatus or supraspinatus fossae, is common in patients
interface does not recapitulate the organized anatomy or structure of with chronic, larger rotator cuff tears134. The acromioclavicular joint,
the native enthesis. Lineage tracing studies suggest that even in acute anterior capsule, coracoid process, posterior capsule, bicipital groove
reattachment, the native enthesis is replaced with scar-forming cells and acromion are palpated for tenderness135. Most patients with rotator
leading rather to a mechanically inferior attachment127. cuff tears will not report tenderness in these areas, but they should be
Healing at the enthesis follows the typical reparative cascade of assessed for concomitant pathology.
inflammation, proliferation and remodelling128. Pro-inflammatory A comprehensive assessment of shoulder range of motion is per-
cytokines released by platelets from the clot recruit macrophages, formed. The cervical spine should be examined to rule out pain coming
neutrophils and tendon-derived cells to initiate the repair response. primarily from a spine condition. Cervical spine pathology typically
The proliferative phase of collagen and extracellular matrix deposition presents with a history of radiating pain down past the shoulder and
by recruited fibroblasts results in an increase in cellularity and collagen into the hand, or associated numbness and tingling in a neurological
deposition. During this time, there is also an increase in vascularity. This distribution. During examination of the shoulder, forward flexion,
is followed by remodelling, in which there is a subsequent reduction of abduction, internal rotation and external rotation are evaluated from
cellularity and vascularity that is accompanied by a shift from type III the adducted position (that is, with the patient’s arm at the side). Inter-
collagen to type I collagen, and morphological reorganization and nal and external rotation should also be performed with the shoulder
realignment of the collagen to respond to mechanical loads. abducted to 90° with the elbow flexed to 90° to check for early arthritis
and frozen shoulder — both conditions cause loss of active and passive
Molecular mediators. A myriad of cytokines, including IGFs, VEGF, motion136.
PDGF and members of the TGFβ family, regulate the production of col- The strength of the rotator cuff muscle is also assessed at this step.
lagen and extracellular matrix during the reparative and remodelling Abduction strength is tested with the patient’s arms abducted at 90°

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a Impingement b Partial rotator cuff tear c Full thickness rotator cuff tear
Torn cuff
Partial tear
Bursitis
Humeral
head Humeral
Rotator cuff head
intact
Fig. 4 | Surgical anatomy of rotator cuff tears. Arthroscopic images of rotator In partial-thickness tears, there is fraying of the rotator cuff, but the attachment
cuff impingement (part a), partial-thickness tears (part b) and full-thickness of the tendon to the greater tuberosity is largely intact. In full-thickness rotator
tears (part c). In impingement, inflammatory tissue is present above the intact cuff tears, the rotator cuff is detached from the humeral head. In this example,
rotator cuff, with increased vascularity and tissue in the subacromial space. the tear is large with retraction of the rotator cuff to the glenoid rim.
and forward-flexed at 30° to be in the plane of the supraspinatus137. Several tests are also available to assess the subscapularis muscle
Weakness in this position (measured manually with applied downward and tendon. The shoulder must be placed in an internally rotated
pressure) can be indicative of a supraspinatus tear. External rotation position prior to testing to eliminate the strength of the pectoralis.
strength is tested with the patient’s arm adducted and the elbow flexed The lift-off test (Gerber test) is performed by placing the arm in an
to 90°. Weakness with external rotation can be indicative of a tear of the internal rotated position behind the patient’s back138. The dorsum of the
infraspinatus and/or teres minor, which is almost always accompanied hand is placed at the base of the lumbar spine and the patient is asked
by a supraspinatus tear that has extended posteriorly. The patient can to lift the hand off the back and hold the position. The strength of the
also be assessed for a painful arc — the patient must raise the arms above manoeuvre is assessed by the examiner by applying counter-pressure
the head and bring the arms down slowly to the sides. In a positive to the hand. An inability to lift the hand off the back or inability to
test, the patient reports pain during the 120° movement down to the resist the examiner’s counter-pressure represents a positive test140,141.
40° angle. This test is the most sensitive in patients with a rotator cuff The belly press test evaluates subscapularis function: in a standing or
problem; however, the test cannot differentiate between tendinopathy, seated position, the patient’s arm is abducted ~20–30° with the arm
partial-thickness tear and full-thickness tear138. internally rotated and elbow flexed to 90°. The patient is instructed
to press the palm of the hand into the abdomen while keeping the ipsi-
Physical examination tests. Although several well-described tests lateral elbow in the abducted starting position. The patient not being
can aid the examiner in diagnosing rotator cuff pathology. These able to perform the manoeuvre or the elbow falling to the patient’s side
tests lack high sensitivity and specificity and, therefore, must be used during the attempted press indicates a positive test140,142,143.
in conjunction with history and imaging to establish an accurate diag- No single test is diagnostically accurate, but the combination of
nosis. The Neer test is performed with the examiner standing behind manoeuvres, and correlation with symptoms, facilitates an accurate
the patient with the affected arm passively elevated with the examiner’s diagnosis of rotator cuff pathology. However, distinguishing the spec-
hand stabilizing the scapula. Pain at maximal forward flexion is often trum of impingement to partial-thickness to small full-thickness tears
indicative of rotator cuff pathology137,139. In the Hawkins–Kennedy test, remains challenging. Nevertheless, large tears and those with loss of
the affected arm is passively elevated to 90° of forward flexion and the the force couple from tears that extend through the rotator cuff cable55
elbow is placed at 90° of flexion in the neutral position. The forearm is are readily diagnosed owing to profound weakness of the shoulder
then turned into internal rotation, which brings the greater tuberosity (pseudoparesis) and by a positive external rotation lag sign138,144.
into contact with the undersurface of the acromion. Pain with internal
rotation is suggestive of rotator cuff pathology137,140. The Jobe test is Radiography. Imaging is an important diagnostic tool for evaluating
performed to assess the strength of the supraspinatus. The patient the severity of rotator cuff pathology. Multiple imaging modalities
places the arm at 90° of abduction and 30° of flexion in the plane of allow non-invasive diagnosis of rotator cuff tears and can provide key
the scapula. Shoulder elevation is manually resisted by the examiner. information to determine the most appropriate and effective treatment
Pain or weakness denotes a positive test140,141. Furthermore, the drop options. Imaging evaluation should begin with plain radiographs of
arm test can also be used to assess the supraspinatus muscle. The the shoulder, as they are inexpensive and accessible, and can provide
patient’s arm is passively abducted to 90° and the patient then slowly information regarding acute bony injury or confirm the presence
lowers the straight arm to the side (adducted position). Inability to of concomitant degenerative joint disease, which influences initial
control the descent of the arm or pain reported during this manoeuvre management. Key findings from imaging include the degree of rotator
constitutes a positive test138–140. cuff tear arthropathy145; degenerative or proliferative changes at the

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Table 1 | Differential diagnosis of rotator cuff pathology decisions, although the reproducibility of this system is moderate at
best163–165. Advanced MRI techniques, such as IDEAL MRI and Dixon fat–
Diagnosis Clinical symptoms or key physical examination findings water separation sequences, can allow a more precise measurement of
Rotator cuff Impingement signs intramuscular fat that allows improved treatment recommendations
degeneration Neer test (sensitivity 72–78%, specificity 58–60%) compared with findings from conventional MRI89,166–169. Information
Hawkins–Kennedy test (specificity 79–92%, sensitivity 25–57%) obtained from preoperative MRI can be utilized in scoring systems,
Painful arc test (positive likelihood ratio 3.7) such as the rotator cuff healing index, which offer insight into the
Supraspinatus Painful arc test (positive likelihood ratio 3.7) likelihood of success after surgical treatment170. Magnetic resonance
tear Jobe test (sensitivity 69–88%, specificity 30–62%) arthrography has excellent diagnostic performance and is an additional
Drop arm test (sensitivity 8–12%, specificity 92–100%) option for imaging, although the addition of intra-articular contrast
material is often not necessary for the routine evaluation of rotator
Subscapularis Pain or weakness with lift-off test (sensitivity 25–100%,
tear specificity 50–94%) cuff tears155,171. In areas with limited MRI availability, availability of
Pain or weakness with belly press test (sensitivity 34–73%, arthroscopic surgical resources might also be limited, making overall
specificity 72–96%) diagnosis and treatment of rotator cuff pathology very challenging.
Large rotator External rotation lag sign (positive likelihood ratio 7.6)
cuff tears Weakness with muscle testing (all groups)
CT. CT is less frequently utilized than other imaging modalities for
the diagnosis of rotator cuff tears. The Goutallier classification was
Other common shoulder pathologies
originally developed based on CT imaging. Although CT can provide an
Frozen Limited active and passive range of motion (no radiographic evaluation of muscle quality, a detailed analysis of soft tissue employing
shoulder signs of glenohumeral arthritis)
a CT scan is limited161. For patients who do not have access to MRI, a CT
Glenohumeral Limited active and passive range of motion (radiographic arthrogram can be an option to evaluate the rotator cuff; extension of
arthritis signs of glenohumeral arthritis) contrast material into the subacromial space indicates a full-thickness
SLAP tear O’Brien test rotator cuff tear172.
Biceps Painful at bicipital groove
tendonitis Yergason test Ultrasonography. Ultrasonography can offer excellent information
Speed test regarding all clinically relevant aspects of rotator cuff injuries, while
also being low-cost, portable and more comfortable for patients
AC joint Tenderness at AC joint
degeneration than MRI173–175. Ultrasonography can detect partial-thickness and
Cross-body test
full-thickness rotator cuff tears, with specificity ranging from 0.77 to
Cervical spine Radiating pain past elbow 0.98 (refs. 155,176,177). Ultrasonography can be utilized to determine
degeneration Spurling test
rotator cuff tear size, retraction and muscle quality16,178. Although
AC, acromioclavicular; SLAP, superior labrum anterior posterior. ultrasonographic evaluation can be operator-dependent, this modal-
ity can be an excellent, low-cost first-line option for evaluating the
greater tuberosity and at the undersurface of the acromion146,147 and rotator cuff173.
signs of osteoarthritis148,149. An acromiohumeral interval of <6 mm
suggests a chronic full-thickness rotator cuff tear150. Radiographs can Prevention strategies
also effectively diagnose conditions such as greater tuberosity frac- When developing prevention strategies for the development of rota-
tures, calcific tendinopathy and shoulder osteoarthritis, which may tor cuff tears, it is important to understand that not all risk factors
have overlapping symptoms with rotator cuff disease but different are modifiable. However, strategies should minimize not only the
treatment pathways148,151–153. development of rotator cuff pathology but also symptoms. Postural
training, flexibility programmes and simple strengthening exercises
MRI. MRI offers a comprehensive three-dimensional evaluation of for the shoulder and scapular muscles can be beneficial in improving
the rotator cuff and has high diagnostic performance in detecting shoulder health179. These strategies might help to minimize the risk of
partial-thickness and full-thickness rotator cuff tears, with sensitivity developing poor posture or form, which can lead to compensation and
and specificity values ranging from 0.8 to 0.97 (refs. 154,155). Images undue pressure on an ageing rotator cuff, leading to injury. However,
from MRI can provide an accurate assessment of clinically relevant studies have not shown a clear link between improving posture and
measurements that help predict the likely success of surgical repair, minimizing the incidence of cuff tear and, therefore, the benefits of
including tear size156 and tendon retraction157, and depict the pres- better posture remain theoretical.
ence of associated injuries of the acromioclavicular joint, labrum and Although flexibility and rotator cuff exercises can be beneficial in
glenohumeral cartilage158. A fat-sensitive sagittal–oblique sequence the prevention of symptoms, studies have shown that excessive repeti-
is essential for evaluating the rotator cuff muscle quality, which is tive use of the rotator cuff can be detrimental180. The repetitive nature
most commonly performed clinically with the Fuchs modification of of overhead sports is a well-known factor that contributes to rota-
the Goutallier classification159. The Goutallier classification grades tor cuff symptoms, although how progression to full-thickness tears
muscle quality from 0 to 4: 0 indicates normal muscle with no fat, occurs is unclear. Limiting the time spent engaged in repetitive exer-
1 indicates streaks of fat in the muscle, 2 indicates more muscle than cises and activities, careful biomechanical evaluation of performance
fat, 3 indicates equal proportions of muscle and fat, and 4 indicates and a continual emphasis on form are the most effective p reventative
more fat than muscle in the expected muscle location159. Muscle quality, measures to avoid symptoms arising from a rotator cuff tear.
especially of the infraspinatus, is predictive of surgical outcomes after Smoking cessation programmes are imperative before any surgi-
rotator cuff repair160–162. The Goutallier classification impacts clinical cal intervention to circumvent its negative effect on healing. Chronic

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inflammation, which are observed in individuals with diabetes mellitus deltoid strengthening, teres minor strengthening for active external
and obesity can contribute to tendon injury181. Although no clear dietary rotation, scapular stability and control exercises, patient education,
change can prevent rotator cuff tears, following an anti-inflammatory adaptation, proprioception and a home exercise programme191.
diet (for example, foods that are high in anti-oxidants such as blueber-
ries, almonds and fatty fish) may aid in alleviating pain and inflamma- Medical management
tion associated with rotator cuff injuries. Further research investigating Pharmacotherapy, including medications such as acetaminophen,
the role of anti-inflammatory diet is necessary182. In animals, vitamin D NSAIDs and corticosteroids, can be used for short-term pain relief in
deficiency may affect the ability of an acutely injured rotator cuff to patients with symptomatic rotator cuff tears. If no contraindications
heal following surgery. Hence, screening for and treating vitamin D exist, acetaminophen is commonly used as the first-line medication and
deficiency may be beneficial183. Evidence shows a possibility of longer NSAIDs are suggested for intermittent use as a second-line treatment.
duration of symptoms and a worse prognosis in patients with depres- Oral and topical NSAIDs can effectively relieve shoulder pain secondary
sion and anxiety than in those without. Patients should be screened to tear if used for a short time period (4–8 weeks)196,197 and have been
to identify those with these common pathologies so that they can be shown to be safe preoperatively and postoperatively198. The adverse
counselled to improve outcomes184. effects of these medications should be taken into consideration when
used as long-term treatment.
Management Subacromial corticosteroid injections (CSIs) are recommended
The goals of management are to reduce pain and enable return to in the inflammatory stage or early stages of rotator cuff tears to
function, including improved sleep. In asymptomatic patients or in reduce pain and improve function in patients with moderate-to-
those with minimal shoulder symptoms, observation alone might be severe pain and in those who failed initial physical therapy and/or
sufficient. These patients should be made well aware of the risks of oral anti-inflammatory drugs. CSIs can be effective in the short term,
progression, with pain serving as a key marker of likely tear progression especially for small tears, and CSIs in combination with physical therapy
over time and an indicator warranting evaluation and treatment. can successfully reduce pain and improve function within 6 weeks.
This combination can allow some patients to avoid surgery altogether.
Physical therapy If not successful after 6 weeks of treatment, the long-term efficacy of
The predominant treatment modality in patients with symptomatic rota- CSIs is limited. Importantly, preoperative CSIs may be associated with
tor cuff tendinopathy, or partial-thickness or full-thickness tears is phys- increased rates of postoperative infections and revision surgery if
ical therapy. Physical therapy is effective and when successful, results administered within 1 month of surgery199–201. Furthermore, the admin-
in quicker return to activities and function than surgical treatment185. istration of two or more CSIs the year before surgery substantially
The MOON Shoulder Group followed 381 patients (31–90 years increases the risk of subsequent revision rotator cuff surgery199.
of age; mean age 62 years) with atraumatic full-thickness rotator cuff
tears over 2 years, and demonstrated substantial improvements in Platelet-rich plasma
patient-reported outcomes (PROs) including American Shoulder Many studies have investigated platelet-rich plasma (PRP) as a potential
and Elbow Surgeons (ASES) scores and a reduced rate of surgery after non-operative treatment for rotator cuff tears and have shown mixed
physical therapy186. Patients undertook 6–12 weeks of a standardized results regarding the effectiveness of these injections. The studies
supervised physical therapy programme focusing on basic rotator cuff showed reduced pain and improved function in patients with tendi-
strengthening and shoulder mobility, and >70% of the patients demon- nopathy at 6 months with deterioration to baseline levels by 1 year202.
strated improvements in PROs and were satisfied with non-operative A meta-analysis in 2023 demonstrated that PRP was equivalent to CSIs
management. Importantly, belief that physical therapy would improve in terms of pain relief and function at any given time point203. In addi-
their symptoms was the most important factor in predicting the suc- tion, these studies showed substantial variability in the number of PRP
cess of therapy187. Several other randomized studies have shown similar injections, injection volume and platelet concentration. According to
outcomes comparing physical therapy and surgical intervention with the 2019 clinical practice guidelines from the American Academy of
short-term and mid-term follow-up188,189, although long-term PROs may Orthopaedic Surgeons, evidence is limited to support the routine use
favour surgery in some patients at 10 years after presentation190. Even of PRP for treating cuff tendinopathy or partial-thickness tears and,
in the setting of massive tears, a deltoid muscle rehabilitation regimen currently, PRP is not indicated for the treatment of full-thickness tears.
is effective in improving function and pain191.
The goal of physical therapy is restoration of full, pain-free Mesenchymal stem cells
range of motion, flexibility, muscle balance and scapulothoracic and The advent of MSCs has opened new potential avenues for therapeutic
glenohumeral muscular control and stability. Improving scapular interventions for rotator cuff tears. This technique involves the injec-
stability, proper neuromuscular control of the shoulder girdle and tion of MSCs into the rotator cuff tendon or into the subacromial bursa.
thoracic posture are essential in a well-designed rotator cuff exercise Studies have shown significant improvements in pain and functional
programme192,193. Potential contributing mechanisms to abnormal outcomes in patients treated with MSCs compared with placebo, but
scapular kinematics include pain, soft-tissue tightness, altered muscle further research assessing mid-term and long-term outcomes is needed
activation or strength imbalances, muscle fatigue and poor thoracic to standardize their use204. Moreover, the use of culture-expanded
posture194,195. Studies have shown tightness of the pectoralis minor MSCs is not approved by the FDA and, therefore, these cellular treat-
and posterior glenohumeral capsular stiffness in relation to abnormal ments are only available in the USA within an Investigational New Drug
scapular position. Rehabilitation exercises to stretch the posterior cuff application or FDA-regulated randomized control trial.
and pectoralis minor and reduce upper trapezius activation are recom- Proper patient counselling and careful patient selection are crucial
mended to improve soft-tissue tightness and allow optimal scapular when considering non-operative management of rotator cuff tears.
motion. For larger tears, physiotherapy should focus on active anterior Educating the patient to understand that non-operative treatment

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typically does not result in a complete ‘cure’ or healing of the tear is no consensus on the optimal technique, which is likely to depend on
despite symptom improvement is important. Although conservative tear configuration and so-far-undefined patient-specific factors228.
management can successfully treat most patients with rotator cuff Although the biomechanical properties and retear rates of double-row
tears, ~25% of patients progress to need surgical intervention. suture bridge repair are better than simple single-row repair229–231,
clinical outcomes according to repair technique are not significantly
Surgical intervention different232.
Subacromial decompression including acromioplasty is a widely per- The use of orthobiologics, such as MSCs intraoperatively has
formed procedure to treat subacromial impingement syndrome205,206. shown promising results to decrease retear rates233. In a prospective
Despite the theoretical advantages of acromioplasty, its role in pain study234, bone marrow aspirate concentrate augmentation resulted in
management and/or prevention of progression to rotator cuff tear is still a 39% decrease in retear rate at 1 year compared with a control group
a matter of debate. Several randomized trials found superiority of acro- who underwent rotator cuff repair only. For PRP, several studies have
mioplasty to exercise therapy alone207,208; however, long-term follow-up shown improved healing rates, particularly in larger tears, but clinical
studies found no significant differences in clinical outcomes209–213. outcomes are not improved by PRP augmentation235–238. Although PRP
All-arthroscopic rotator cuff repair is considered the treatment of may enable some early mobilization and pain relief, the long-term
choice for rotator cuff tears that fail non-operative management or for outcomes are comparable to those following well-performed rota-
acute traumatic rotator cuff tears. However, retear remains an unsolved tor cuff repair239,240. The clinical evidence for the use of PRP in the
problem, reported for 10–40% of procedures214. Short-term outcomes non-operative management of rotator cuff disorders is inconsistent,
are favourable regardless of retear; however, in many patients with making inferences difficult. Furthermore, in one study in patients with
retear, long-term outcomes are worse than in patients without retear rotator cuff tears managed with arthroscopic surgical repair, there was
and deteriorate over time215–217. no difference in clinical and imaging outcomes at 10 years follow-up
To prevent retear, accurate prediction of reparability and healing between those receiving and those not receiving PRP injections241. The
after repair is important. Predictors of retear can be classified as tear wide range of effectiveness can be related to the types of PRP used and
characteristic factors and patient demographic factors. Tear charac- the variability in preparation techniques, cell counts and growth factors
teristic factors include tear size170,218–220, fatty infiltration and muscle available242. These differences make it necessary to plan adequately
atrophy221. These factors could decrease the elasticity and vitality of powered appropriately standardized studies with clinically relevant
the rotator cuff tendon tissues, inhibiting healing after rotator cuff outcome measures.
repair221,222. Old age, diabetes, osteoporosis, dyslipidaemia, obesity In patients with an irreparable tear, when retracted tendons can-
and smoking are demographic risk factor for retear170,218,222–225. Using a not be re-attached to the greater or lesser tuberosity without arthritic
15-point scoring system to predict healing after cuff repair170 (Table 2), change of the glenohumeral joint, other treatment options are con-
retear rate in patients with ≤4 points was 6.0%; however, rates in those sidered, especially in young, active patients. These include partial
with ≥5 and ≥10 points were 55.2% and 86.2%, respectively. repair, superior capsular reconstruction (reconstructing the superior
Given the high retear rates, there has been considerable focus on capsule using allograft or autogenic tensor fascia lata), an allogenic or
improving the biomechanical and biological construct of the repair. The xenogenic patch bridging graft, muscle advancement (releasing the
ideal biomechanical suture configuration for rotator cuff repair proximal rotator cuff muscle to re-attach to the footprint), tendon
requires mechanical stability until tendon-to-bone healing occurs, transfer, subacromial balloon spacer, and other procedures243–246.
without excessive tension, which can damage the repaired tendon226,227. Results with these diverse treatment strategies are mixed, as expected
To achieve this goal, several repair techniques are employed but there in small case series with complex conditions.
If the rotator cuff tear is assumed to be irreparable in older
patients and/or if accompanied by arthritic change of the gleno-
Table 2 | 15-point scoring system to predict healing after humeral joint, reverse shoulder replacement is the primary treatment
arthroscopic rotator cuff repair option247. Reverse shoulder arthroplasty reverses normal anatomy, so
that the glenoid has the ‘ball’ side (glenosphere on the glenoid side)
Factor Points
articulating with the humeral cup (metal tray with polyethylene insert).
Demographics This technique has excellent long-term outcomes for irreparable cuff
Age >70 years 2 tears and cuff tear arthropathy247,248. The 10-year success rate of reverse
shoulder arthroplasty is up to 93%, but functional outcomes deterio-
Bone mineral density T-score ≤−2.5 2
rate over time, particularly in patients >80 years of age249–251. Various
Level of work activity high 2 complications related to reverse shoulder including scapular acro-
Tear characteristics mial notching, instability, infection and glenoid loosening can occur
Anteroposterior direction tear size >2.5 cm 2 (at rates of 1–5%)252–257.
An overall algorithm for treatment is presented in Fig. 5. Rotator
Mediolateral direction tear size (retraction) <1 cm 0
cuff repairs with concomitant moderate-to-severe glenohumeral osteo-
Mediolateral direction tear size (retraction) 1 to <2 cm 1 arthritis had worse outcomes than rotator cuff tears with mild gleno-
Mediolateral direction tear size (retraction) 2 to <3 cm 2 humeral osteoarthritis258. Thus, reverse shoulder arthroplasty in patients
Mediolateral direction tear size (retraction) ≥3 cm 4
with rotator cuff tear with concomitant moderate-to-severe osteoar-
thritis classified as grade ≥2 using the Samilson–Prieto classification
Infraspinatus fatty infiltration Goutallier grade ≥2 3
is the treatment of choice, especially in those >65 years old148,258.
Using this algorithm, retear rates of patients with ≤4 points were 6.0%; however, those with ≥5 If the degenerative arthritic change is mild (Samilson–Prieto clas-
and ≥10 points were 55.2% and 86.2%, respectively170.
sification grade ≤1)148, the healing potential of the rotator cuff repair is

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Evaluation of arthritis using radiography

Fig. 5 | Algorithm for rotator cuff tear treatment.
Patients with a known rotator cuff tear are evaluated
with radiographs. Patients with advanced arthritis
(Samilson–Prieto (S-P) grade 2–4) are treated
S-P grade 1 S-P grade ≥2
with either conservative management (physical
therapy or steroid injections) or reverse shoulder
arthroplasty (RSA). In patients with minimal arthritis
RoHI ≤4/15 RoHI >4/15 Age <65 years Age ≥65 years
(S-P grade 1), treatment is determined by the rotator
cuff healing index (RoHI)170. A score of >5/15 suggests
Measure AHD using radiography with and without load Conservative treatment a lower likelihood of healing, and the acromial
humeral distance (AHD) is measured as a sign of
chronic superior humeral head migration. If the AHD
AHD difference ≥3.2 mm AHD difference <3.2 mm Failed is <3.2 mm, then surgical treatment should be an
RSA. In patients with a RoHI score of <5/15, or an AHD
of >3.2 mm, a rotator cuff repair is recommended.
Small tears can be treated with several options
including simple sutures or a modified Mason–
Rotator cuff repair RSA
Allen repair. For larger tears and massive tears,
greater tuberosity (GT) coverage dictates either
Intraoperatively measure the tear size and repair tension a double row suture bridge or single row repair to
reduce tension on the repair. Irreparable tears can
be treated with RSA, tendon transfers or another
Small sized tear Medium-to-large sized tear Massive tear procedure such as a biceps transfer or balloon
arthroplasty.
GT coverage without GT coverage without

excessive tension ≥50% excessive tension <50%
Double row suture Tension-free single row repair with or without

Modified Mason–Allen technique bridge technique medialization
considered. To predict healing potential, utilization of the aforemen- Long-term outcomes

tioned 15-point scoring system including age, bone mineral density, Non-surgical management. Relatively few studies have investigated
level of work activity, tear size and fatty infiltration of the infraspinatus the long-term quality of life and overall outcomes in patients treated
might be helpful170,259 (Table 2). In patients with rotator cuff tear with a non-operatively for full-thickness rotator cuff tear. For example, in
score of ≤4, repair should be considered. In patients with a score of >4, one study that followed 93 patients for five or more years, 25 patients
X-ray can evaluate whether there is fixed humeral head elevation260. (27%) had undergone surgery at the latest follow-up. Of 63 patients
If the acromiohumeral elevation is fixed and not reversible, reverse who completed the rotator cuff quality of life (RC-QOL) questionnaire,
shoulder arthroplasty should be considered as the treatment option. those treated non-operatively scored 83 out of 100 points and those
treated surgically scored 89 out of 100 (ref. 270). Isolated full-thickness
Quality of life supraspinatus tears seem to respond well to non-operative manage-
Rotator cuff tears of all sizes and cuff tear arthropathy can be painful ment in the long term, with reasonable overall outcomes and lim-
with the potential to compromise motion, strength and function261,262. ited progression of fatty infltration271. Tear progression seems to be
By contrast, structural change to the rotator cuff can be identified in a associated with recurrent or deteriorating symptoms and, therefore,
large proportion of individuals (~60 years of age) who never complain some patients who initially respond well to non-surgical treatment
of shoulder pain or loss of function263. Hence, the effect of rotator cuff may undergo surgery in the future. In a long-term randomized con-
disease on well-being remains difficult to analyse. trolled trial, the non-operative group did not do as well as the surgically
Psychosocial and mental health problems are associated with repaired group at 10 years, suggesting that, in younger or more active
greater symptoms and worse function in patients with symptomatic patients, repair may be preferred190, a concept that was supported in
rotator cuff disease than in patients without mental health issues33,264,265. a propensity-matched study272.
Whether the rotator cuff disease is further disabling because of worse
mental coping mechanisms or if the chronicity of rotator cuff disease Surgical rotator cuff repair. Several studies have shown substantial
leads to psychological and mental dysfunction in these individuals improvements in pain, function and quality of life following rotator cuff
remains unclear. Regardless of causation, anxiety, depression and repair261,273,274. Improvements in quality of life after surgery seem to be
similar disorders seem to negatively impact non-operative and surgi- maintained in the long term261,275. Interestingly, and rather perplexing,
cal outcomes. In addition, rotator cuff disease is associated with sleep a large number of patients who became and remained asymptomatic
disturbance266–268, which is common even more than a year after rotator after rotator cuff repair showed evidence of persistent thinning of
cuff repair269. the repaired site or even structural failure of the rotator cuff repair on

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imaging, indicating that the repaired tendons never completely heal MSCs and bone marrow aspirate concentrate, to improve tendon–bone
despite improvements in pain, motion, function and quality of life261. healing and tendinopathy. Preliminary findings from experimental
Several long-term studies suggest that healing is important and, if models and clinical studies are encouraging but are in the early stages
repair integrity is intact, the outcomes at 10–15 years after surgery of research281,282.
are excellent276,277. A population of MSCs reside in the subacromial bursa, which are
responsive to inflammatory stimuli, indicating an as-yet-unexplored
Reverse shoulder arthroplasty. Reverse shoulder arthroplasty pro- biological role in the context of rotator cuff disease283. Bursa–tendon
vides substantial improvements in pain, function and quality of life in crosstalk has an interesting clinical relevance and could be a novel
many individuals with an irreparable cuff tear, particularly cuff tear target in the management of shoulder disorders. Indeed, using a rat
arthropathy278,279. Reverse shoulder arthroplasty is particularly useful model of rotator cuff injury and repair, proteomic profiling of the
when the subscapularis and the posterosuperior cuff are irreparable, bursa demonstrated increased cytokine expression and MSC pro-
as well as in the presence of associated arthritis. However, a subset liferation after rotator cuff tears, probably to protect the adjacent
of patients — individuals with an irreparable cuff tear, no arthritis intact tissue and to maintain the morphology of the underlying bone65.
and good preoperative active motion — are particularly at risk of The bursa, therefore, may have an initiating and essential role in heal-
dissatisfaction after reverse arthroplasty280. ing by acting as a potential cellular source to promote healing after
repair81.
Outlook Collagen injections have been used to treat rotator cuff tendi-
Several important unmet needs remain in the field of rotator cuff nopathy and to support arthroscopic repair. Their mechanism of action
degeneration and repair (Box 3). Much of the focus of ongoing research is not completely understood, but they have been hypothesized to
revolves around using orthobiologics such as PRP, growth factors, induce regenerative pathways, to stimulate tenocyte proliferation and
migration, and to increase endogenous collagen synthesis to restore
collagen fibres in damaged tendons284–287. Integrin receptors in fibro-
Box 3 blasts are activated and, consequently, the growth factor cascade
initiates the synthesis of endogenous collagen, healing the damaged
collagen fibres and leading to proper alignment288–292. Despite the use
Unmet needs in the treatment of different types of collagens and injection protocols, or applying
different PROs, studies have shown clinically and functionally relevant
of rotator cuff pathology improvements.
Novel surgical procedures to improve outcomes of rotator cuff
Basic science repair are consistently being attempted, but management of large
•• Determine the pathophysiology of rotator cuff pain and massive tears remains a considerable challenge. In patients with
•• Understand the molecular pathways responsible for tendon massive rotator cuff tears (>5 cm), repair of the superior capsule as well
degeneration as the rotator cuff has been reported to improve retear rates at early
•• Develop strategies to improve the biological basis of tendon–bone follow up293,294. The superior capsule defect has been defined as the
healing essential lesion of rotator cuff tears295, and several researchers recom-
•• Understand the relationship and pathophysiology of muscle mend its repair to restore shoulder biomechanics, preventing the rise
degeneration of the humeral head in the postoperative period296,297. It is also thought
•• Develop pharmacological strategies to enhance muscle quality to provide an additional source of autologous tenocytes, which may
after rotator cuff repair improve the biology of the repair.
The long head of the biceps tendon, that is rich in tenocytes and
Diagnosis and management fibroblasts, is a major stabilizer of the humeral head preventing supe-
•• Evaluate genetics of rotator cuff disease — is it preventable at all? rior migration and reinforcing repair298–300. Its use for cuff repair may
•• Predictive modelling of who will benefit from surgery versus provide a local autologous source of collagen, and can be incorporated
non-operative management in the repair arthroscopically with no further surgical exposure or
•• Predictive modelling of tear onset and progression donor site morbidity298.
•• Determine pathophysiology of tendon degeneration in specific Optimal management of shoulder disability may be influenced
disease states (for example, diabetes mellitus) by the more detailed understanding of the natural history of disease
and the anticipated operative outcomes. Machine learning employs
Perioperative and postoperative computer algorithms and statistical analysis to determine complex
•• Predictive modelling of surgical outcomes trends and patterns, which can be difficult to perform in a clinical set-
•• Develop strategies to choose optimal repair configuration ting. Studies have shown promising results in accurately predicting
or biological augmentation postoperative scores. This methodology may be improved to support
•• Optimize salvage options (tendon transfer, reverse, etc.) preoperative counselling, planning and resource allocation301.
for irreparable tears Overall, rotator cuff pathology is a substantial clinical problem
•• Improve muscle quality after repair with physical therapy with room for improvements in our understanding of pathophysiology,
modalities and future research should focus on methods to optimize outcomes
•• Accelerate recovery after surgery of treatment.
•• Improve sleep after surgery
Published online: xx xx xxxx

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inhibiting range of motion: a biomechanical analysis. Arthroscopy 34, 2590–2600 Competing interests
(2018). The authors declare no competing interests.
300. Schmalzl, J. et al. Tendon-derived stem cells from the long head of the biceps tendon:
inflammation does not affect the regenerative potential. Bone Joint Res. 8, 414–424 Additional information
(2019). Peer review information Nature Reviews Disease Primers thanks A. Carr; N. Jain, who
301. Potty, A. G. et al. Approaching artificial intelligence in orthopaedics: predictive analytics co-reviewed with R. Prakash; and the other, anonymous, reviewer(s) for their contribution
and machine learning to prognosticate arthroscopic rotator cuff surgical outcomes. to the peer review of this work.
J. Clin. Med. 12, 2369 (2023).
302. Akhtar, A., Richards, J. & Monga, P. The biomechanics of the rotator cuff in health Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims
and disease – a narrative review. J. Clin. Orthop. Trauma. 18, 150–156 (2021). in published maps and institutional affiliations.
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Introduction (B.T.F. and A.B.); Epidemiology (J.K. and P.M.); Mechanisms/pathophysiology
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Rotator cuff tears

Article in Nature Reviews Disease Primers · February 2024

Drew A. Lansdown Nicola Maffulli

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Rotator cuff tears

by primary care and orthopaedic surgeons, with a spectrum ranging Epidemiology

Rotator cuff tears begin as degenerative changes within the tendon,

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Anterior view Posterior view

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have been linked to rotator cuff disease, no studies have examined

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Rotator cuff spectrum of disease

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tendons, possibly secondary to inflammation and abnormal oxidative

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b Subacromial spur Pectoralis muscle

Tendon biology PG, GAG and collagen content

Genetic Polymorphism of collagen,

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Evaluation of arthritis using radiography

GT coverage without GT coverage without

Double row suture Tension-free single row repair with or without

considered. To predict healing potential, utilization of the aforemen- Long-term outcomes

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