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Is tendon pathology a continuum? A pathology model
to explain the clinical presentation of load-induced
tendinopathy
J L Cook,1 C R Purdam2
1
Centre for Physical Activity and ABSTRACT modulated by an interaction between intrinsic
Nutrition Research, School of Overuse tendinopathy is problematic to manage clinically. factors such as genes, age, circulating and local
Exercise and Nutrition Sciences,
People of different ages with tendons under diverse loads cytokine production, sex, biomechanics and body
Deakin University, Melbourne,
Australia; 2 Department of present with varying degrees of pain, irritability, and composition.
Physical Therapies, Australian capacity to function. Recovery is similarly variable; some Although loading history and individual factors
Institute of Sport, Canberra, tendons recover with simple interventions, some remain may influence the onset and amount of tendon
Australia pathology, these are not generally considered when
resistant to all treatments.
Correspondence to: The pathology of tendinopathy has been described as developing a treatment plan for painful tendons.
Dr Jill Cook, 221 Burwood degenerative or failed healing. Neither of these descrip- Treatment for a first-time presentation of tendino-
Highway, Melbourne 3025, tions fully explains the heterogeneity of presentation. This pathy in a young athlete is often the same as that
Australia; jill.cook@deakin.edu. offered to a postmenopausal woman with chronic
au review proposes, and provides evidence for, a continuum
of pathology. This model of pathology allows rational tendinopathy. The model proposed in this paper
Accepted 18 August 2008 placement of treatments along the continuum. hypothesises that the pathology and the response
Published Online First A new model of tendinopathy and thoughtful treatment to treatment are different in these presentations,
23 September 2008 implementation may improve outcomes for those with and that interventions should be tailored to the
tendinopathy. This model is presented for evaluation by pathology. Applying a single intervention to all
clinicians and researchers. presentations of tendinopathy is unlikely to be
efficacious in every case.
This paper will examine existing concepts of
Overuse tendon injury (tendinopathy) occurs in tendinopathy and then present a model for the
loaded tendons of the upper and lower limb and pathological process in tendon that collates exist-
results in pain, decreased exercise tolerance of the ing knowledge. The model will be based on
tendon and a reduction in function. Characteristic evidence from clinical and basic science studies in
changes occur in tendon structure, resulting in a humans to demonstrate its validity.
tendon that is less capable of sustaining repeated
tensile load. EXISTING TENDON PATHOLOGY CONCEPTS
Tendon injury can occur in the mid-tendon, as in At least three states of tendon pathology have been
the Achilles tendon; however, most tendon pathol- described to date. Following the demise of a
ogy and pain arise at the tendon attachment to primary inflammatory model, tendinopathy was
bone, such as the patellar tendon, medial and considered to be degenerative. Degenerative tendi-
lateral elbow tendon and tendons of the groin. nopathy is described variably; pathological terms
While the mid-tendon and the insertion are such as hypoxic degeneration, hyaline degeneration
morphologically different in the normal state, the and mucoid degeneration are used, all of which
onset of pathology induces cell matrix changes that suggest non-reparative, end-stage pathology.6 The
are indistinguishable; that is, the pathology key features of degenerative pathology centre on
appears to be the same.1 Despite a similar irreversible, degenerative cell changes and disinte-
pathology, it has been shown in the Achilles that gration of the matrix.
exercise specific for insertional or mid-tendon Other authors have suggested that injured
tendinopathy provides improved clinical outcomes, tendon is in a healing phase, with active cells and
probably a reflection of the loading profiles in increased protein production, but with disorgani-
different parts of the tendon.2 3 sation of the matrix and neovascularisation. This
Load has been shown to be both anabolic and has been called failed healing7 or angiofibroblastic
catabolic for tendons.4 Repetitive energy storage hyperplasia.8
and release and excessive compression appear to be Failed healing and degeneration have been
key factors in the onset of tendinopathy. The associated with chronic overload, but pathology
amount of load (volume, intensity, frequency) that has also been described when a tendon is unloaded
induces pathology is not clear; however, sufficient (stress-shielded). Unloading a tendon induces cell
time between loadings to allow a tendon to and matrix change similar to that seen in an
respond to load appears important. Therefore overloaded state9 and decreases the mechanical
volume (hours) and frequency (sessions per day integrity of the tendon.10 In animals, this state has
or week) of intense load may be critical in the been shown to be mostly reversible11; however, few
capacity of both normal and pathological tendons human studies have been conducted and tendon
to tolerate load.5 Although load is a major patho- unloading will not be considered further in this
aetiological component, it is almost certainly paper.

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Despite these varied descriptions of tendon pathology, the Clinically, reactive tendinopathy results from acute overload,
possibility that these may be linked in a continuum has received usually a burst of unaccustomed physical activity. Reactive
limited consideration.12 If a model of pathology can be tendinopathy can also be seen clearly after a direct blow such as
developed that is continually evaluated and modified in the falling directly onto the patellar tendon.15 This non-tensile, and
light of research findings, a better understanding of tendon only transiently compressive, load induces considerable reaction
pathology, treatment and prevention is possible. within the tendon cell and matrix.
Evidence that reactive tendinopathy occurs in response to
overload is fairly strong from in-vitro work.16 There is a
A NEW MODEL OF TENDON PATHOLOGY
homogeneous, non-inflammatory cell response to load that
We propose that there is a continuum of tendon pathology that
leads to metaplastic change in the cells and cell proliferation.
has three stages: reactive tendinopathy, tendon dysrepair (failed
Tendon cells become more chondroid in shape, with more
healing) and degenerative tendinopathy (fig 1). The model is
cytoplasmic organelles for increased protein production. The
described for convenience in three distinct stages; however, as it
primary proteins are large proteoglycans, and this results in
is a continuum, there is continuity between stages.
matrix change due to an increase in bound water associated
Adding or removing load is the primary stimulus that drives
with these proteoglycans. Collagen integrity is mostly main-
the tendon forward or back along the continuum, especially in
tained, although there can be some longitudinal separation, and
the early stages. Within the constraints of recovery proposed in
there is no change in neurovascular structures.
the model, reducing load may allow the tendon to return to a
These initial changes in ground substance in reactive
previous level of structure and capacity within the continuum.13
tendinopathy may occur because quick adaptation is necessary
until longer-term change in either structure or mechanical
What are the pathological, imaging and clinical manifestations at properties (true adaptation) happens. The quick response is
each stage? possible as larger proteoglycans associated with tendinopathy
1. Reactive tendinopathy (aggrecan and versican) and some glycoproteins (hyaluronan)
It is proposed that reactive tendinopathy, a non-inflammatory can be upregulated in a timespan varying from minutes to a few
proliferative response in the cell and matrix, occurs with acute days, much more quickly than the small proteoglycans of
tensile or compressive overload. This results in a short-term normal tendon (20 days).17
adaptive and relatively homogeneous thickening of a portion of Thus, reactive response is a short-term adaptation to overload
the tendon that will either reduce stress (force/unit area) by that thickens the tendon, reduces stress and increases stiffness.
increasing cross-sectional area or allow adaptation to compres- The tendon has the potential to revert to normal if the overload
sion. This differs from normal tendon adaptation to tensile load, is sufficiently reduced or if there is sufficient time between
which generally occurs through tendon stiffening with little loading sessions.
change in thickness.14
Imaging
The tendon is swollen in a fusiform manner; the diameter is
increased on both magnetic resonance imaging (MRI) and
ultrasound (US) scans. Ultrasound shows reflection from intact
collagen fascicles, with diffuse hypoechogenicity occurring
between intact collagen structures. Magnetic resonance imaging
will show minimal or no increased signal at this stage. The
change in imaging appearance is mainly derived from the
increase in bound water within the proteoglycans (fig 2).

Clinical
Reactive tendinopathy is seen clinically in an acutely overloaded
tendon and is more common in a younger person. For example,
a young jumping athlete who dramatically increases the
number of jumping/landing repetitions a week may develop
patellar tendon swelling and pain.
Tendons chronically exposed to low levels of load (e.g. in the
detrained athlete returning from illness or injury, or a sedentary
person) may also be vulnerable to this stage of tendinopathy
when exposed to moderate increase in load. In addition it may
occur as a result of direct trauma to tendon, to which the
Achilles, patellar and elbow tendons are particularly exposed.

2. Tendon dysrepair
Tendon dysrepair describes the attempt at tendon healing,
similar to reactive tendinopathy but with greater matrix
breakdown. There is an overall increase in number of cells,
Figure 1 Pathology continuum; this model embraces the transition which are mainly chondrocytic, as well as some myofibroblasts,
from normal through to degenerative tendinopathy and highlights the resulting in a marked increase in protein production (proteogly-
potential for reversibility early in the continuum. Reversibility of can and collagen). The increase in proteoglycans results in
pathology is unlikely in the degenerative stage. separation of the collagen and disorganisation of the matrix.

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Figure 2 (A) Ultrasound image of a
thickened patellar tendon with intact
collagen fascicles. The arrow indicates
the width of the tendon. (B)
Histopathological appearance of reactive
tendinopathy/early tendon dysrepair. Note
the increased cell numbers and
intermittent cell rounding with some
evidence of increased ground substance
(light blue shading) (histology picture by
courtesy of F Bonar).

The changes are somewhat more focal and matrix changes more intratendinous signal. The changes are more focal rather than
varied than in the reactive stage. There may be an increase in spread throughout the tendon.
vascularity and associated neuronal ingrowth.18
Clinical
Imaging This stage is primarily seen in the older person, but is seen in a
The imaging changes reflect increased matrix disorganisation, younger person or elite athlete with a chronically overloaded
and these tendons are swollen, with increasing evidence of tendon. The classic presentation is a middle-aged, recreational
collagen disorganisation. On US there is some discontinuity of athlete with focal Achilles tendon swelling and pain. The
collagen fascicle and small focal areas of hypoechogenicity. The tendon can have one or more focal nodular areas with or
increase in vascularity may be evident on colour or power without general thickening. Individuals with degenerative
Doppler, and techniques to enhance vascularity (heat, exercise, changes often have a history of repeated bouts of tendon pain,
hanging the limb) (personal communication, Cormick, 2008) often resolving but returning as the tendon load changes.
may show a greater number of vessels. On MRI the tendon is Degenerative tendinopathy, if extensive enough, or if the
swollen and there is increased signal within the tendon. tendon is placed under high load, can rupture,22 consistent with
97% of tendons that rupture having degenerative change.23
Clinical
This pathology has been reported in chronically overloaded EVIDENCE TO SUPPORT THIS MODEL
tendons in the young,19 but may appear across a spectrum of As longitudinal monitoring of histopathological change in
ages and loading environments. This stage may be hard to humans is ethically difficult, the stages and progressions
distinguish clinically; these tendons are thick with more suggested in this model have been derived from integrating
localised changes in one area of the tendon. Tendon dysrepair evidence from cross-sectional studies and supported by findings
is best detected when imaging detects some focal structural in animal models. Limited weight has been placed on outcomes
changes with or without increased vascularity. in animal studies, as animal tendons do not directly translate to
The frequency, volume or length of time over which load has human tendinopathy. Longitudinal imaging studies in humans
been applied (ie, months or years of overload) may be important allow tracking of tendon change over time, and these
variables. An older person with stiffer tendons that have less demonstrate that some transition up and down the proposed
adaptive ability may develop this stage of tendinopathy with pathology model occurs. Finally, limited evidence is available
relatively lower loads. Some reversibility of the pathology is still from clinical studies.
possible with load management and exercise to stimulate The concepts embedded in this model are strikingly similar to
matrix structure.20 those reported for articular cartilage pathology.24 In osteoar-
thritis Pollard et al proposed a continuum from a reversible stage
through to advanced osteoarthritis (table 1). The initial
3. Degenerative tendinopathy
response centred on reversible proteoglycan upregulation, initial
This stage is clearly described in the literature, with progression
swelling and cellular upregulation, through to the latter stages
of both matrix and cell changes.8 Areas of cell death due to
of irreversible heterogeneous tissue change including cell and
apoptosis, trauma or tenocyte exhaustion are apparent.21 As a
cartilage degeneration and erosion and subchondral bone
result, areas of acellularity have been described, and large areas
remodelling.
of the matrix are disordered and filled with vessels, matrix
breakdown products and little collagen. There is little capacity
for reversibility of pathological changes at this stage. There is Histopathological studies
considerable heterogeneity of the matrix in these tendons, with Evaluation of human asymptomatic tendons demonstrated that
islands of degenerative pathology interspersed between other cell change was always present when matrix change became
stages of pathology and normal tendon. apparent.25 Additionally, matrix change was primarily in ground
substance, followed by collagen, and then (theoretically but not
demonstrated) in vascularity. This provides evidence for the
Imaging progression from normal to reactive response and tendon
The compromised matrix and the vascular changes can be dysrepair; however, this study did not examine tendons that
extensive. These appear on ultrasound scans as hypoechoic would be classified as degenerative. Although not considered a
regions with few reflections from collagen fascicles. Numerous good model for human overuse tendinopathy, animal studies
and larger vessels are usually visible on Doppler US. Magnetic support these findings. Scott et al16 reported similar progression
resonance imaging demonstrates increased tendon size and in pathology in overloaded rat supraspinatus tendons.

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Table 1 Stages of osteoarthritis tendons in jumping athletes demonstrate that they primarily
transition towards abnormality and pain that is more apparent
Feature Reversible injury Osteoarthritis Ageing
in adults31 than in adolescents.32
Cartilage mass Hypertrophy Hypertrophy, No Change
erosion
Cartilage Focal Focal. General, all layers Clinical studies
topographic Heterogeneous The cumulative effect of load on a tendon has been clearly
distribution
demonstrated when the tendon health of athletes who placed
Cartilage water Oedema Oedema Dehydration
high loads on their Achilles tendons in early adulthood was later
Cartilage collagen Reversible Degradation Increased advanced
deformation glycation end evaluated. Previous elite athletes had a higher cumulative
products incidence of tendinopathy and rupture than age-matched
Cartilage Reversible Irreversible Reduced synthesis controls.33 As rupture represents end-stage degenerative tendi-
proteoglycan depletion depletion nopathy,23 the higher rupture rates support high chronic load as
Cartilage matrix Resorption Accumulative, Accumulative: an important factor in tendon pathology. This also supports the
degeneration collagen, oxidation. Glycation,
products proteoglycan amyloid non-reversible nature of degenerative pathology, as these older
Cell activity Reversibly Increased activity Reduced ex-athletes had not spontaneously recovered tendon health.
increased and proliferation The inability of a tendon to recover once it reaches the
Synovium Mid focal Mid focal superficial Atrophy degenerative stage is supported by studies that have examined
superficial inflammation
tendons many years after injury or rupture. Although the
inflammation
Bone No Change Subchondral Osteopenia
tendons may improve their function, they do not appear to
remodelling return to normal size or morphology. Several studies have
Reproduced with permission and copyrightß of the British Editorial Society of Bone
shown that large hypoechoic areas do not change,34–36 and
and Joint Surgery. Pollard et al, 2008. The assessment of early osteoarthritis. J Bone similarly tendons used for anterior cruciate ligament graft
Joint Surg Br;90-B:411–21. replacements remain abnormal for years.37

Degenerative tendinopathy has been extensively described, but

the transition from dysrepair has not been demonstrated.
PLACING CLINICAL TREATMENTS IN THE PATHOLOGY MODEL
Deciding where a tendon is in the pathological spectrum
For ease of use clinically, we have divided the pathology into
Imaging studies two clear groups: reactive/early tendon dysrepair and late
Acute tendon response tendon dysrepair/degenerative. This will allow most clinical
An acute bout of exercise increased the MRI volume and signal tendon presentations to be clearly placed in one of the two
in abnormal Achilles tendon.26 This suggests several critical categories based on clinical assessment.
things: tendon response is rapid, and tendon response is to Clinical and imaging features allow a tendon to be placed in
increase volume (circumference) and water (either bound as one of these two categories. An older person with a thick
part of ground substance or in vessels). This is the earliest form nodular tendon is likely to have a degenerative tendon;
of the reactive response to load proposed in this model. conversely, a young athlete after acute overload with a fusiform
swelling of the tendon will probably have a reactive tendino-
Normal to reactive, and back pathy. There are, however, tendons in which it may be clinically
Several studies demonstrate both short-term and long-term difficult to stage the pathology, and in these tendons imaging
changes in the imaging appearance of tendons. Nearly half of may give vital clues. If the tendon is generally swollen and
normal patellar tendons (with pain) became abnormal (mainly mildly hypoechoic or has small focal hypoechoic areas (one or
reactive tendinopathy) in the presence of ongoing load over a several) with no or minimal vascular changes, this indicates
season of volleyball (high tendon load). A single tendon became reactive/early tendon dysrepair (fig 2). Tendons with large
hypoechoic, suggesting transition through a reactive tendino- discrete areas of hypoechogenicity, multiple vessels and more
pathy to tendon dysrepair/degenerative tendinopathy.27 focal swelling will be in the late tendon dysrepair/degenerative
Longitudinal imaging studies have consistently demonstrated category (fig 3).
that between 10% and 30% of tendons reported as abnormal at This division of a continuum into two categories allows us to
baseline become normal at follow-up.28–30 This supports the have a nominal threshold beyond which tendons will not fully
viability of a transition from reactive change back to normal return to normal structure. Cell dysfunction or death that
tendon. compromises matrix protein production and/or the inability of
the matrix to regain structural integrity results in a tendon
Reactive to dysrepair incapable of full repair. It has been demonstrated that even after
In a group of young athletes at risk of tendon overload and improvement in Achilles tendon pain and tendon structure and
pathology there was a subgroup with microhypoechoic areas on vascularity after an eccentric exercise programme, the tendon
US.19 This may represent a transition from reactive to tendon remains thicker than normal for several years.20
dysrepair, where small islands of the tendon develop collagen
disorganisation. There is little evidence of reversal of this PLACING PAIN IN THIS MODEL OF TENDINOPATHY
transition in the longitudinal studies to date. Pain can occur at any point in this pathological model,
supporting the well-known dissociation between pain and
Dysrepair to degenerative tendinopathy pathology in tendinopathy. Even tendons that appear normal
This transition is not clearly demonstrated in the literature, as on imaging can be painful.27 Conversely, two-thirds of tendons
they are both considered abnormal and are not often identified degenerative enough to rupture have been reported to be pain-
as separate entities. Imaging evaluation of highly loaded patellar free before rupture.23

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Figure 3 (A) Ultrasound of a normal
right and tendon dysrepair/degenerative
left patellar tendon. Note the vessel
evident on power Doppler in the left
tendon, the hypoechoic area and the
tendon swelling. (B) Histopathological
appearance of late tendon dysrepair/
degeneration. Note the markedly
increased cell numbers, the loss of
collagen evidenced by the loss of
longitudinal rows of cells, and the
increase in vessels (histology picture by
courtesy of F Bonar).

The source of pain has been associated with neurovascular the matrix to resume a more normal structure. Also, a tendon
ingrowth,38 seen in this model at the late tendon dysrepair/ with reduced load is likely to have less pain. Identifying and
degenerative phase. However, the fact that tendons can be painful changing the abusive load may be as simple as allowing a day or
or pain-free anywhere in this model suggests another or two between high or very high tendon loads. Assessment and
supplementary cause of pain that has so far proved elusive. The modification of the intensity, duration, frequency and type of
presence of biochemical substances stimulated by overload load is the key clinical intervention. This may include
(compression or tension) and/or acting on sensitised nerves in identifying the potential for biomechanical overload. Studies
matrix seems to be one possibility. Cell production of substances show that tendon response in type 1 collagen precursors peaks
such as catecholamines, acetylcholine and glutamate acting on around 3 days after a single bout of intense exercise, suggesting
their receptors, which allow autocrine/paracrine signalling, has that time interval for adaptive response is an important factor.41
been described,39 which may explain pain in the cellularly active Tendon load without energy storage and release, such as cycling
stages in this model: reactive and tendon dysrepair. or strength-based weight training, can be maintained, as this is
Pain is the single clinical feature that the clinician seeks to less likely to induce further tendon response. Conversely, high-
change, and pain response to treatment is a key indicator of load elastic or eccentric loading, particularly with little recovery
treatment success. If pain levels and response to load are time (eg, on successive days), will tend to aggravate tendons in
considered with the stage of pathology, treatment progression this stage.
and outcomes may improve.
Tendinopathic pain is induced by load and has two key Pharmacotherapies
features: (1) dose-dependent pain in relation to singular or Non-steroidal anti-inflammatory medications (NSAIDs) have
cumulative load, and (2) pain that is well localised to the tendon been reported to retard soft tissue healing in a range of tissues.
or enthesis. Increasing load on the tendon will usually increase Although pain may be reduced, they have a negative effect on
pain. During assessment, the tendon should be provocatively tendon repair.42 In reactive tendinopathy, this may be a
loaded to functional levels to fully evaluate the level of pain. preferred effect, as tenocyte upregulation and excess ground
Pain should be assessed in the context of the stage and level of substance expression are apparent in this phase of tendino-
pathology; an extensively degenerated tendon with mild pain pathy.25 Ibuprofen (as well as indomethacin and naproxen
can have insufficient integrity to tolerate high loads and has a sodium) has been shown to inhibit expression of key ground
risk of rupture. Conversely, a proliferative tendinopathy is more substance proteins responsible for tendon swelling (aggrecan) in
reactive and therefore assessment needs to be more conservative in-vitro tendon preparations.43 Ibuprofen and celecoxib are also
when loading during assessment. reported to have a specific effect in downregulating the cellular
response.44 45 Ibuprofen may be favoured as it has not been
TREATMENT OF TENDINOPATHY shown to have a detrimental effect on ultimate tendon repair.42
Clinical treatments directed at effecting change in tendon Corticosteroids, primarily used to decrease pain, also decrease
structure or pathology are considered optimal interventions, but, cell proliferation and protein production and therefore could be
as pain is often the clinical presentation, a case can be made for used in the reactive painful tendon. Repeated peritendinous
concentrating on reduction of pain as a valid outcome. It is evident corticosteroid has been shown to reduce tendon diameter at 7
that pain can occur anywhere in the pathological continuum; and 21 days after injection in tendons.46 Although peritendinous
interventions that reduce pain and are also appropriate for the injection is clinically accepted, it is not known whether
stage of pathology should, therefore, be our ideal. Conversely, peritendon injection induces cell and matrix change within
inappropriate treatments for the stage of pathology (such as the tendon.
‘‘loading up’’ of a tendon in the proliferative phase of tendino-
pathy) may increase pain, leading to a poor clinical outcome.40 Late tendon dysrepair/degenerative tendinopathy
Common interventions and their proposed place in this model are
Physical treatments
summarised in table 2. In an effort to maintain clarity of approach,
Treatments that stimulate cell activity, increase protein
polymodal interventions, often undertaken in the clinical manage-
production (collagen or ground substance) and restructure the
ment of tendinopathy, have not been considered.
matrix are appropriate for this stage of tendinopathy. Exercise
interventions are discussed separately below.
Reactive tendinopathy/early tendon dysrepair Frictions have been proposed as an effective treatment in
Physical treatments tendon injury, and the rationale for their use, based on improving
At this stage load management (reduction) will generally allow tendon structure, fits into this stage of tendon pathology. They
the tendon time to adapt, the cells to become less reactive and have been shown to increase protein production in animals,47 but

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Table 2 Clinical and pharmacological treatments placed in the model Glyceryl trinitrate has been shown to effectively reduce
tendon pain in addition to the benefits of eccentric exercise.69–71
Stage Pharmacological management Physical management
It is reported to deliver increased amounts of nitric oxide to the
Reactive Tenocyte inhibitors (ibuprofen, Load management. injured tendon, leading to improvement in collagen synthesis,
tendinopathy/early celecoxib, corticosteroid), aggrecan Reduction in frequency ¡
tendon dysrepair inhibitors (ibuprofen, naproxen intensity of tendon load
although a recent study has not demonstrated increased tissue
sodium, indomethacin) levels of NO or benefit from the treatment.72 These studies have
Late tendon Prolotherapy (including blood), Exercise with eccentric not examined the long-term effect of this treatment on tendon
dysrepair/ aprotinin, sclerosing therapy, component, ESWT, structure or tendon vascularity.
degeneration glyceryl trinitrate frictions, ultrasound
ESWT, extracorporeal shock wave therapy.
PLACING EXERCISE IN THIS MODEL
Exercise, particularly eccentric exercise, has been shown to
in humans few stringent investigations have been conducted,48
affect both tendon structure and pain. Eccentric exercise has
and the results are variable. Clinically, compared with exercise,
been shown to increase collagen production in abnormal
frictions were less effective in reducing pain.49
tendons but not in normal tendons.73 Eccentric exercise has
Extracorporeal shock wave therapy (ESWT) has been shown
been shown to improve tendon structure in both the short
to have pain-relieving effects in a number of tendons, although
term74 and the longer term20 and decrease tendon vessels.75
ESWT is not consistently shown to be superior to placebo Eccentric exercise is an effective pain-relieving treatment, with
treatment. Studies in animal tendons show variable morpholo- pain changing in the first 4–6 weeks.76 A meta-analysis reported
gical and mechanical benefits and detriments from this that eccentric exercise is beneficial for pain, function and return
modality, but it may be of benefit in this stage of pathology.50 to activity.77
Ultrasound has been shown to increase protein production at In this model, for athletes in an earlier stage of tendinopathy,
a tissue level.51 Similarly to frictions, it is less effective than who are already loading the tendon in a significant manner,
exercise in treating patellar tendinopathy.49 52 adding exercise (painful or not) may not improve outcome.41 78
Surgery for chronic painful (presumably degenerative) ten- This model hypothesises that exercise is a potent stimulus to
dons has produced varied outcomes, with 50–80% of athletes the already upregulated tendon cells and overstimulates a
able to return to sport at their previous level.53–55 Although fundamentally intact, but reactive (or sensitised), matrix. In
surgical techniques vary considerably, their results are not degenerative tendinopathy, exercise appears to be a positive
dissimilar.56 Outcome after surgery was no better than eccentric stimulus for cell activity and matrix restructuring.
exercise57or ESWT58 for patellar tendinopathy. Surgery in non- In degenerative tendons, exercise-based treatments allow
athletic people produced poorer results than in active people.59 variable levels of pain. The Alfredson eccentric exercise
Despite these outcomes, surgery is considered a reasonable programme suggests that pain during exercise in this stage
option in those who have failed conservative interventions. may be tolerated by the tendon.79 This is supported by
Silbernagel et al, whose study in a similar population allowed
Pharmacotherapies activity pain of less than 5/10 during activity.80 There was no
Treatments that stimulate a healing response in the tendon are difference in outcome when compared with a group that just
appropriate for degenerative tendinopathy. The injection of exercised without continuing activity. These studies suggest
various substances around or into the tendon or the process of that exercise that induces pain in the degenerative stage will not
injection itself has been proposed to achieve this. affect outcome. If pain in degenerative tendinopathy is
Prolotherapy using glucose and blood injections stimulates a mediated by neurovascular structures more than cellular
tissue response. Blood injection stimulates cell proliferation and products, as this model suggests, then neurovascular pain
production of vascular endothelial growth factor,60 and it has appears to be less reactive and tendons would be less irritable
been demonstrated to induce matrix changes. Clinically, blood in this stage of tendinopathy.
injections have led to reduced vascularity and decreased tendon
diameter on ultrasound.61 DISCUSSION
Injection itself, regardless of the substances injected, has been We present a simple and succinct model of tendon pathology,
shown to have a beneficial effect on tendon structure. Multiple which is consistent with the clinical presentations of tendino-
tendon biopsies improved structural outcome in degenerative pathy. The aim of this model is to logically order treatment
tendons at 1 year compared with an untreated group,62 and options for clinicians. Although we have used the term load-
injections of active (polidocinol) and placebo (anaesthetic and induced tendinopathy, we have deliberately not detailed what
adrenaline) substances produced similar outcome.63 type of load is responsible. Debate on the relative contribution
Aprotinin, a collagenase inhibitor, may preserve collagen in a of tensile, compressive and combined loads is for other fora.
remodelling matrix. A recent randomised placebo-controlled Although these are presented as discrete stages of pathology,
trial did not show benefits of aprotinin over placebo,64 although it is highly probable that some tendons may have discrete
earlier studies have shown an effect on pain.65 regions that are in different stages at the one time. Examination
Sclerosing therapy has repeatedly been shown to be effective of tissue, particularly in the latter stages of pathology, often
in treating pain and improving structure in tendinopathy.66 reveals heterogeneous pathology in a single tendon.81 It is
When compared with placebo, both pain and structural possible that a tendon with degenerative change that is acutely
outcomes were significantly better with the sclerosing treat- overloaded may develop reactive change in previously normal
ment in both Achilles and patellar tendon.67 Interestingly, the parts of the tendon. Evaluating these more complex presenta-
effect on vessels appears to be delayed, with vascularity tions has deliberately not been discussed in this paper to
increasing in the short term after treatment, suggesting that maintain simplicity. Improving capacity to clinically evaluate
the positive effect on pain may be through chemical neurolysis and treat these more difficult tendons is primarily dependent on
rather than vascular change.68 accepting the basic model presented.

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Research into tendinopathy may also be improved by 8. Kraushaar B, Nirschl R. Tendinosis of the elbow (tennis elbow). Clinical features and
findings of histological, immunohistochemical, and electron microscopy studies.
considering this model. It is possible that the variable response J Bone Joint Surg Am 1999;81-A:259–78.
to tendon treatment in research studies may be explained to 9. Ohno K, Yasuda K, Yamamoto N, et al. Effects of complete stress-shielding on the
some extent through the existence of subpopulations of mechanical properties and histology of in situ frozen patellar tendon. J Orthop Res
different pathologies in the investigated cohort. In fact, the 1993;11:592–602.
10. Kubo K, Akima H, Ushiyama J, et al. Effects of 20 days of bed rest on the
most consistent outcomes in research appear to occur when the viscoelastic properties of tendon structures in lower limb muscles. Br J Sports Med
participants are clearly in one group, such as in Alfredson’s 2004;38:324–30.
eccentric exercise research on older, presurgical patients. 11. Yamamoto N, Hayashi K, Kuriyama H, et al. Effects of restressing on the mechanical
properties of stress-shielded patellar tendons in rabbits. J Biomech Eng
Very little research has been conducted in early-stage 1996;118:216–20.
tendinopathy, possibly because of the inherent capacity of 12. Neer CS. Impingement lesions. Clin Orthop Related Res 1983;173:70–7.
these tendons to spontaneously recover, the variability of pain 13. Cook JL, Khan KM, Kiss ZS, et al. Asymptomatic hypoechoic regions on patellar
presentation and the difficulties in assembling a sizeable cohort. tendon ultrasound: A 4-year clinical and ultrasound followup of 46 tendons.
Scand J Med Sci Sports 2001;11:321–7.
The individual factors considered earlier (genes, age, circulat- 14. Magnusson SP, Narici MV, Maganaris CN, et al. Human tendon behaviour and
ing and local cytokine production, sex, biomechanics and body adaptation, in vivo. J Physiol 2008;586:71–81.
composition) may alter the progression forward or back in the 15. Garau G, Rittweger J, Malliaras P, et al. Traumatic patellar tendinopathy. Disability
and Rheumatism 2008;30:1616–20.
continuum82 and most are also likely to have an important role
16. Scott A, Cook JL, Hart DA, et al. Tenocyte responses to mechanical loading in vivo:
in the response to treatment in tendinopathy. For example, A role for local IGF-I signaling in early tendinosis. Arthritis and Rheumatism. In press.
some athletes appear completely resistant to tendinopathy 17. Samiric T, Ilic MZ, Handley CJ. Characterisation of proteoglycans and their catabolic
despite high loads, and have never been shown to progress into products in tendon and explant cultures of tendon. Matrix Biol 2004;23:127–40.
18. Danielson P, Alfredson HK, Forsgren S. Distribution of general (PGP 9.5) and sensory
proliferative tendinopathy. Conversely, other athletes sustain (substance P/CGRP) innervations in the human patellar tendon. Knee Surg Sports
tendon ruptures relatively early in their careers, presumably Traumatol Arthrosc 2006;14:125–32.
after some degenerative change in the tendon. Identifying 19. Cook JL, Khan KM, Kiss ZS, et al. Patellar tendinopathy in junior basketball players: A
athletes at risk of tendon pathology, as well as using this model controlled clinical and ultrasonographic study of 268 patellar tendons in players aged
14–18 years. Scand J Med Sci Sports 2000;10:216–20.
in treatment, may improve outcomes. Early load management 20. Ohberg L, Lorentzon R, Alfredson H. Eccentric training in patients with chronic
in at-risk athletes may keep them in the early stages of tendon Achilles tendinosis: normalised tendon structure and decreased thickness at follow
pathology and limit progression. up. Br J Sports Med 2004;38:8–11.
21. Lian O, Scott A, Engebretsen L, et al. Excessive apoptosis in patellar tendinopathy in
Time to recovery should be inherent in a clinical model such
athletes. Am J Sports Med 2007;35:605–11.
as this; however, the capacity for tendons to transition up and 22. Nehrer S, Breitenseher M, Brodner W, et al. Clinical and sonographic evaluation of
down between stages makes time estimates for recovery the risk of rupture in the Achilles tendon. Arch Orthop Trauma Surg 1997;116:14–18.
difficult. Overall, tendons respond very slowly, both in 23. Kannus P, Jozsa L. Histopathological changes preceding spontaneous rupture of a
tendon. A controlled study of 891 patients. J Bone Joint Surg Am 1991;73:1507–25.
improving load capacity and in resolving pain. 24. Pollard T, Gwilym S, Carr A. The assessment of early osteoarthritis. J Bone Joint
Surg Br 2008;90-B:411–21.
25. Cook JL, Feller JA, Bonar SF, et al. Abnormal tenocyte morphology is more prevalent
CONCLUSIONS than collagen disruption in asymptomatic athletes’ patellar tendons. J Orthop Res
This model explains most clinical presentations and most 2004;22:334–8.
findings in the tendon literature. It can even encompass primary 26. Shalabi A, Kristoffersen-Wiberg M, Aspelin P, et al. Immediate Achilles tendon
response after strength training evaluated by MRI. Med Sci Sport Exerc
collagen tearing83 and some form of inflammation underpinning 2004;36:1841–6.
the cell and matrix response. Emerging mechanisms for injury, 27. Malliaras P, Cook J. Patellar tendons with normal imaging and pain: Change in
complex interactions between the cell and matrix and systemic imaging and pain status over a volleyball season. Clin J Sports Med 2006;16:388–91.
and local factors (growth factors, cytokines and treatments) will 28. Cook J, Kiss Z, Khan K, et al. Prospective imaging study of asymptomatic patellar
tendinopathy in elite junior basketball players. J Ultrasound Med 2000;19:473–9.
need to be built into this model. The integrity of the model will 29. Fredberg U, Bolvig L. Significance of ultrasonographically detected asymptomatic
only be as good as its capacity to withstand additional research. tendinosis in the patellar and achilles tendons of elite soccer players: a longitudinal
This model now requires scientific and clinical evaluation. study. Am J Sports Med 2002;30:488–91.
30. Khan KM, Cook JL, Kiss ZS, et al. Patellar tendon ultrasonography and jumper’s knee
Funding: Jill Cook was funded by a Club Warehouse Visiting Fellowship to the in female basketball players: A longitudinal study. Clin J Sport Med 1997;7:199–206.
Australian Institute of Sport Physical Therapies department. Club Warehouse had no 31. Malliaras P, Cook J. Prospective study of change in patellar tendon abnormality on
direct or indirect involvement in the production of this manuscript. imaging and pain over a volleyball season. Br J Sports Med 2005;40:272–4.
32. Gisslen K, Alfredson H. Neovascularisation and pain in jumper’s knee: a prospective
Competing interests: None declared. clinical and sonographic study in elite junior volleyball players. Br J Sports Med
2005;39:423–8; discussion 423–8.
33. Kujala UM, Sarna S, Kaprio J. Cumulative incidence of achilles tendon rupture and
REFERENCES tendinopathy in male former elite athletes. Clin J Sport Med 2005;15:133–5.
1. Maffulli N, Testa V, Capasso G, et al. Similar histopathological picture in males with 34. Adriani E, Mariani PP, Maresca G, et al. Healing of the patellar tendon after
Achilles and patellar tendinopathy. Med Sci Sport Exerc 2004;36:1470–5. harvesting of its mid-third for anterior cruciate ligament reconstruction and evolution
2. Fahlstrom M, Jonsson P, Lorentzon R, et al. Chronic Achilles tendon pain treated of the unclosed donor site defect. Knee Surg Sports Traumatol Arthrosc 1995;3:138–
with eccentric calf-muscle training. Knee Surg Sports Traumatol Arthrosc 43.
2003;11:327–33. 35. Karjalainen PT, Aronen HJ, Pihlajamaki HK, et al. Magnetic resonance imaging
3. Jonsson P, Cook J, Alfredson H. New regimen for eccentric calf muscle training in during healing of surgically repaired Achilles tendon ruptures. Am J Sports Med
patients with chronic insertional Achilles tendinopathy: Results of a pilot-study. 1997;25:164–71.
Br J Sports Med 2008;42:746–9. 36. Sanchis-Alfonso V, Subias-Lopez A, Monteagudo-Castro C, et al. Healing of the
4. Benjamin M. Tendons are dynamic structures that respond to changes in exercise patellar tendon donor defect created after central-third patellar tendon autograft
levels. Scand J Med Sci Sports 2002;12:63–4. harvest. Knee Surg Sports Traumatol Arthrosc 1999;7:340–8.
5. Langberg H, Skovgaard D, Asp S, et al. Time pattern of exercise-induced changes in 37. Kiss ZS, Kellaway DP, Cook JL, et al. Postoperative patellar tendon healing: An
Type I collagen turnover after prolonged endurance exercise in humans. Calcif Tissue ultrasound study. VIS Tendon Study Group. Australas Radiol 1998;42:28–32.
Int 2000;67:41–4. 38. Alfredson H. The chronic painful Achilles and patellar tendon: research on basic
6. Jozsa L, Kannus P. Histopathological findings in spontaneous tendon ruptures. biology and treatment. Scand J Med Sci Sports 2005;15:252–9.
Scand J Med Sci Sports 1997;7:113–18. 39. Danielson P, Alfredson HK, Forsgren S. Immunohistochemical and histochemical
7. Clancy W. Failed healing responses. In: W Leadbetter, J Buckwater, S Gordon, eds. findings favoring the occurrence of autocrine/paracrine as well as nerve-related
Sports-Induced Inflammation: clinical and basic science concepts. Park Ridge, Il: cholinergic effects in chronic painful patellar tendon tendinosis. Microsc Res Tech
American Orthopedic Society for Sports Medicine, 1989. 2006;69:808–19.

Br J Sports Med 2009;43:409–416. doi:10.1136/bjsm.2008.051193 415

 Review

Br J Sports Med: first published as 10.1136/bjsm.2008.051193 on 23 September 2008. Downloaded from http://bjsm.bmj.com/ on August 20, 2023 by guest. Protected by copyright.
40. Fredberg U, Bolvig L, Andersen NT. Prophylactic training in asymptomatic soccer 63. Zeisig E, Fahlström M, Öhberg L, et al. Pain relief after intratendinous injections in
players with ultrasonographic abnormalities in Achilles and patellar tendons: the patients with tennis elbow: results of a randomised study. Br J Sports Med
Danish Super League Study. Am J Sports Med 2008;36:451–60. 2008;42:267–71.
41. Langberg H, Skovgaard D, Petersen LJ, et al. Type I collagen synthesis and 64. Brown R, Orchard J, Kinchington M, et al. Aprotinin in the management of Achilles
degradation in peritendinous tissue after exercise determined by microdialysis in tendinopathy: a randomised controlled trial. Br J Sports Med 2006;40:275–9.
humans. J Physiol 1999;521:299–306. 65. Capasso G, Testa V, Maffulli N, et al. Aprotinin, corticosteroids and normosaline in
42. Ferry ST, Dahners LE, Afshari HM, et al. The effects of common anti-inflammatory the management of patellar tendinopathy in athletes: a prospective randomized
drugs on the healing rat patellar tendon. Am J Sports Med 2007;35:1326–33. study. Sports Exercise and Injury 1997;3:111–15.
43. Riley GP, Cox M, Harrall RL, et al. Inhibition of tendon cell proliferation and matrix 66. Lind B, Öhberg L, Alfredson H. Sclerosing polidocanol injections in mid-portion
glycosaminoglycan synthesis by non-steroidal anti-inflammatory drugs in vitro. J Hand Achilles tendinosis: remaining good clinical results and decreased tendon thickness at
Surg Br 2001;26B:224–8. 2-year follow-up. 2006;14:1327–32.
44. Tsai WC, Tang FT, Hsu CC, et al. Ibuprofen inhibition of tendon cell proliferation and 67. Hoksrud A, Ohberg L, Alfredson H, et al. Ultrasound-guided sclerosis of neovessels
upregulation of the cyclin kinase inhibitor p21CIP1. J Orthop Res 2004;22:586–91. in painful chronic patellar tendinopathy: a randomized controlled trial. Am J Sports
45. Tsai WC, Hsu CC, Chou SW, et al. Effects of celecoxib on migration, proliferation and Med 2006;34:1738–46.
collagen expression of tendon cells. Connect Tissue Res 2007;48:46–51. 68. Alfredson HK, Ohberg L. Increased intratendinous vascularity in the early period
46. Fredberg U, Bolvig L, Pfeiffer-Jensen M, et al. Ultrasonography as a tool for after sclerosing injection treatment in Achilles tendinosis : a healing response? Knee
diagnosis, guidance of local steroid injection and, together with pressure algometry, Surg Sports Traumatol Arthrosc 2006;14:399–401.
monitoring of the treatment of athletes with chromic jumper’s knee and Achilles 69. Paoloni J, Appleyard R, Nelson J, et al. Topical glyceryl trinitrate treatment of
tendinitis: a randomized double-blind, placebo-controlled trial. Scand J Rheumatol chronic noninsertional Achilles tendinopathy. J Bone Joint Surg Am 2004;86-A:916–
2004;33:94–101. 21.
47. Gehlsen G, Ganton L, Helfst R. Fibroblast responses to variation in soft tissue 70. Paoloni JA, Appleyard RC, Nelson J, et al. Topical nitric oxide application in the
mobilisation pressure. Med Sci Sport Exerc 1999;31:531–5. treatment of chronic extensor tendinosis at the elbow. Am J Sports Med
48. Wilson JK, Sevier TL, Helfst R, et al. Comparison of rehabilitation methods in the 2003;31:915–20.
treatment of patellar tendinitis. Journal of Sport Rehabilitation 2000;9:304–14. 71. Paoloni JA, Appleyard RC, Nelson J, et al. Topical glyceryl trinitrate application in
49. Stasinopoulos D, Stasinopoulos I. Comparison of effects of exercise programme, the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded,
pulsed ultrasound and transverse friction in the treatment of patellar tendinopathy. placebo-controlled clinical trial. Am J Sports Med 2005;33:806–13.
Clin Rehabil 2004;18:347–52.
72. Kane TP, Ismail M, Calder JD. Topical glyceryl trinitrate and noninsertional Achilles
50. Maier M, Milz S, Wirtz DC, et al. [Basic research of applying extracorporeal
tendinopathy: a clinical and cellular investigation. Am J Sports Med 2008;36:1160–3.
shockwaves on the musculoskeletal system. An assessment of current status]. Der
73. Langberg H, Ellingsgaard H, Madsen T, et al. Eccentric rehabilitation exercise
Orthopade 2002;31:667–77.
increases peritendinous type I collagen synthesis in humans with Achilles tendinosis.
51. Enwemeka CS. Inflammation, cellularity, and fibrillogenesis in regenerating tendon:
Scand J Med Sci Sports 2007;17:61–6.
implications for tendon rehabilitation. Phys Ther 1989;69:816–25.
74. Shalabi A, Kristoffersen-Wilberg M, Svensson L, et al. Eccentric training of the
52. Warden S. Low-intensity pulsed ultrasound for chronic patellar tendinopathy: a
randomised, double-blind, placebo-controlled trial. Rheumatology. In press. gastrocnemius-soleus complex in chronic Achilles tendinopathy results in decreased
tendon volume and intratendinous signal as evaluated by MRI. Am J Sports Med
53. Coleman BD, Khan KM, Kiss ZS, et al. Open and arthroscopic patellar tenotomy for
chronic patellar tendinopathy. A retrospective outcome study. Victorian Institute of 2004;32:1286–96.
Sport Tendon Study Group. Am J Sports Med 2000;28:183–90. 75. Ohberg L, Alfredson H. Effects on neovascularisation behind the good results with
54. Paavola M, Kannus P, Paakkala T, et al. Long-term prognosis of patients with eccentric training in chronic mid-portion Achilles tendinosis? Knee Surg Sports
Achilles tendinopathy. An observational 8-year follow-up study. Am J Sports Med Traumatol Arthrosc 2004;12:465–70.
2000;28:634–42. 76. Roos EM, Engstrom M, Lagerquist A, et al. Clinical improvement after 6 weeks of
55. Tallon C, Coleman B, Khan K, et al. Outcome of surgery for chronic Achilles eccentric exercise in patients with mid-portion Achilles tendinopathy -- a randomized
tendinopathy. Am J Sports Med 2001;29:315–20. trial with 1-year follow-up. Scand J Med Sci Sports 2004;14:286–95.
56. Coleman BD, Khan KM, Kiss ZS, et al. Outcomes of open and arthroscopic patellar 77. Woodley BL, Newsham-West RJ, Baxter GD, et al. Chronic tendinopathy:
tenotomy for chronic patellar tendinopathy: a retrospective study. Am J Sports Med effectiveness of eccentric exercise. Br J Sports Med 2007;41:188–98.
2000;28:1–8. 78. Visnes H, Hoksrud A, Cook J, et al. No effect of eccentric training on jumper’s knee
57. Bahr R, Fossan B, Loken S, et al. Surgical treatment compared with eccentric in volleyball players during the competitive season: a randomized clinical trial.
training for patellar tendinopathy (Jumper’s Knee). A randomized, controlled trial. Clin J Sport Med 2005;15:227–34.
J Bone Joint Surg Am 2006;88:1689–98. 79. Alfredson H, Pietila T, Jonsson P, et al. Heavy-load eccentric calf muscle
58. Peers KH, Lysens RJ, Brys P, et al. Cross-sectional outcome analysis of athletes with training for the treatment of chronic achilles tendinosis. Am J Sports Med
chronic patellar tendinopathy treated surgically and by extracorporeal shock wave 1998;26:360–6.
therapy. Clin J Sport Med 2003;13:79–83. 80. Silbernagel KG, Thomee R, Eriksson BI, et al. Continued sports activity, using a pain-
59. Maffulli N, Testa V, Capasso G, et al. Surgery for chronic Achilles tendinopathy monitoring model, during rehabilitation in patients with Achilles tendinopathy: a
yields worse results in nonathletic patients. Clin J Sport Med 2006;16:123–8. randomized controlled study. Am J Sports Med 2007;35:897–906.
60. Anitua E, Andı́a I, Sanchez M, et al. Autologous preparations rich in growth factors 81. Khan KM, Bonar SF, Cook JL, et al. Histopathology of common overuse tendon
promote proliferation and induce VEGF and HGF production by human tendon cells in conditions: update and implications for clinical management. Sports Med
culture. J Orthop Res 2005;23:281–6. 1999;6:393–408.
61. Suresh SP, Ali KE, Jones H, et al. Medial epicondylitis: is ultrasound guided 82. September AV, Posthumus M, van der Merwe L, et al. The COL12A1 and COL14A1
autologous blood injection an effective treatment? Br J Sports Med 2006;40:935–9. genes and Achilles tendon injuries. Int J Sports Med 2008;29:257–63.
62. Shalabi A, Svensson L, Kristoffersen-Wiberg M, et al. Tendon injury and repair after 83. Arnoczky SP, Lavagnino M, Egerbacher M. The mechanobiological
core biopsies in chronic Achilles tendinosis evaluated by serial magnetic resonance aetiopathogenesis of tendinopathy: is it the over-stimulation or the under-stimulation
imaging. Br J Sports Med 2004;38:606–12. of tendon cells? Int J Exp Pathol 200;88:217–26.

416 Br J Sports Med 2009;43:409–416. doi:10.1136/bjsm.2008.051193