Research Review By Dr. Shawn Thistle©

Date Posted:

August 2010

Study Title:

Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy


Cook JL, Purdam CR

Author's Affiliations:

Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia; Department of Physical Therapies, Australian Institute of Sport, Canberra, Australia.

Publication Information:

British Journal of Sports Medicine 2009; 43: 409-416.

Background Information:

Tendon injuries are extremely common and encountered frequently in all manual medicine settings. The majority of tendon injuries occur subsequent to overuse, essentially meaning that the imposed demands on the tendon have exceeded its load-bearing capacity, resulting in molecular and structural changes to the tendon that reduce its ability to sustain subsequent loads.

Many years ago, the pain in chronic tendon overuse injuries was believed to be the direct result of a chronic inflammatory process, but because inflammatory cells could be consistently demonstrated in damaged tendons, the opinion changed from inflammation (implied by the older term ‘‘tendinitis’’) to degeneration (represented by the newer terms ‘‘tendinosis’’ or “tendinopathy”). To date, a large amount of scientific data has not shown any direct evidence of inflammation in chronic tendinopathy. In fact, leading researchers and contemporary clinicians have suggested abandoning the term “tendonitis” altogether (1, 2).

There is controversy however – although most histologic findings in tendinopathy represent chronic degeneration, regeneration, and microtears of the tendinous tissue, newer studies using immunohistochemistry and flow cytometry have shown inflammatory cells (8).

Clinically, tendinopathies in both the upper and lower extremity can lead to pain, reduced exercise tolerance, impaired function or performance and even disability or lost playing time. These injuries can be challenging to manage, and presentation is extremely variable.

Continuing progressive research in molecular biology and biomechanics has provided valuable new information and has given rise to new hypotheses in chronic tendinopathy. This condition has been described as degenerative and failed healing, yet neither fully explains the observed variability. The goal of this review paper was to discuss these findings in the framework of a new continuum pathology model for load-induced tendinopathies.

Tendinopathy Concepts:

General Considerations:

In general, tendon injuries can occur in the mid-tendon or at the attachment of the tendon to the bone, also called the enthesis. Although the mid-portion and insertion site of tendons are structurally different when normal, the onset of pathology creates cell and matrix alterations that are virtually indistinguishable.

That being said, the reader should be reminded that in some regions (specifically the Achilles) – insertional and mid-portion tendinopathies respond differently to the same treatment intervention.

The Role of Load in Tendon Pathology:

Despite the obvious importance of load in tendon injuries, it is rarely considered when implementing treatment – the authors propose that their model will take this into account and assist the clinician to tailor treatment to the pathology:
  • load has been shown to be both anabolic and catabolic in tendons
  • repetitive energy storage and release and compression are thought to be important contributing factors
  • the amount of load necessary to being a pathological process or cause injury is unknown
  • however, allowing sufficient time intervals between loading sessions seems to be important
  • the role of load in injury genesis is modulated by intrinsic factors such as gender, age, genetics, local cytokine production, biomechanics and body composition
  • it should also be remembered that tendon injury has been induced in the absence of load (also referred to as a stress-shielded condition – unloading a tendon can cause similar changes to those seen in an overload state)
Existing Pathological Concepts:
  • since the demise of the inflammatory model (although as mentioned, controversy still exists), tendinopathy has been considered as a degenerative condition – spawning various pathological terms such as hypoxic degeneration, hyaline degeneration or mucoid degeneration – all suggest a non-reparative, final-stage pathology
  • others have suggested that injured tendons are in a healing flux, with active protein production but disorganized cell structure in the matrix and neovascularization – this has been termed “failed healing” or “angiofibroblastc hyperplasia” (3)
A New Model of Tendon Pathology:

The authors propose the following pathological continuum model that has three phases (each discussed below):
  1. Reactive Tendinopathy
  2. Tendon Dysrepair (failed healing)
  3. Degenerative Tendinopathy
Reactive Tendinopathy:
  • this is a non-inflammatory proliferative response in the cells and matrix occurring after acute or repetitive tensile or compressive load
  • the result is a short-term adaptive and homogenous thickening of a section of the tendon (increased cross-sectional area) that is thought to be an adaptation to deal with compression
  • the initial changes in ground substance and matrix can occur quickly due to the rapid upregulation of larger proteoglycans (aggrecan and versican) and some glycoproteins (hyaluronan) which can occur in minutes up to a few days (note the upregulation times in normal tendons are approximately 20 days) (4)
  • clinically, this will normally result from: 1) acute bursts of unaccustomed physical activity in younger patients; 2) in tendons chronically exposed to low loads that are exposed to a moderate load increase; 3) direct trauma
  • imaging may reveal fusiform swelling (increased diameter) on MRI or diagnostic ultrasound (US)
Tendon Disrepair:
  • is an attempt at tendon healing, similar to reactive tendinopathy but with an increased matrix breakdown
  • overall cell number increases – mainly chondrocytes and myofibroblasts – leading to disorganization of the matrix
  • there may be an increase in vascularity and/or associated neural ingrowth
  • imaging will reveal increased collagen disorganization and discontinuity (on US will represent small focal hypoechoic areas)
  • clinically this may appear across a variety of loading patterns and age groups – overall this may be hard to distinguish
Degenerative Tendinopathy:
  • is well documented in the literature – involving progression in both cell and matrix changes
  • within the tendon, areas of cell death or tenocyte exhaustion are apparent, as large areas of matrix become disordered and filled with vessels, products of matrix breakdown etc.
  • at this stage, it is thought that there is little chance for reversal
  • there are “islands of degenerative pathology interspersed between other stages of pathology and normal tendon”
  • imaging will reveal: hypoechoic areas with few collagen reflections on US, with numerous and larger vessels visible on Doppler US; MRI shows focally increased tendon size and intratendious signal
  • clinically, the classic presentation is a middle-aged recreational athlete with one or more focal nodular areas with or without tendon thickening, preceded by a history of recurrent tendon pain
  • these cases are typically older patients, but can also be seen in a younger patient with a chronically overloaded tendon
  • most tendons that rupture are likely in this stage
Comments and Supporting Literature for this Model:
  • It is very difficult to longitudinally study degenerative changes in human tendons, so this model is derived from the integration of cross-sectional studies with animal evidence.
  • Longitudinal imaging studies have provided evidence that up to 30% of tendons that show reactive change can change back to normal, supporting the idea that the first phase of the model is reversible (5).
  • At this time, there is no convincing evidence of transition back to normal from tendon disrepair.
  • The authors note than some tendons can contain discrete areas that are in different stages of this model at the same time.
  • The authors note that some athletes appear to be completely resistant to tendinopathy despite high loads; conversely, others seem highly susceptible.
Treatment Considerations:

The pain associated with load-induced tendinopathy normally has two distinct characteristics:
  1. a dose-dependent relationship related to a singular or repeated load
  2. localized to the tendon or enthesis
In order to decide which treatment is appropriate, the authors suggest two clear groups based on their model:

1. Reactive/Early Tendon Disrepair - normally a younger athlete with acute overload and fusiform swelling about the tendon:
  • load management (reduction) is paramount to allow cells to become less reactive
  • this could be as simple as allowing 1-2 days between higher loading sessions
  • activities that do not involve tendon energy storage/release can be used – examples include cycling and strength-based weight training
  • eccentric and high load activities should be avoided
  • NSAIDs may reduce pain, but have a deleterious effect on tendon healing (6)
2. Late Disrepair/Degenerative - normally an older athlete with a thickened, nodular tendon:
  • treatments should stimulate cell activity, increase protein production and restructure the matrix
  • friction interventions have been shown to increase protein production in animals, but human evidence is lacking and existing results are variable
  • Extracorporeal Shock Wave Therapy (ESWT) has been shown to reduce pain levels, but has not proven its superiority to placebo treatments in existing trials
  • increasing attention is being paid to injection therapies (blood, medications etc.) – specifically, blood injection has been suggested to increase cell proliferation and production of vascular endothelial growth factor – it has also demonstrated reduced vascularity and tendon diameter on US (7)
  • injection itself, regardless of associated substance, has shown promise for improving tendon structure (RRS note: this may beg the question about the potential benefits of acupuncture?)
  • eccentric exercise has been shown to have beneficial effects on both tendon structure, collagen production and pain in abnormal tendons – other reviews will deal with this topic in more detail
It should be noted that pain can occur at any stage in this model, which supports the well-established dissociation between pain and tendon damage. To illustrate, up to 2/3 of tendons that rupture have been reported as painless prior to the rupture, despite a high prevalence of degenerative changes.

Clinical Application & Conclusions:

The authors of this paper have presented a simple and succinct model for load-induced tendinopathy that appropriately includes contemporary, multidisciplinary literature on this topic.

The authors wisely reiterate that this is merely a model of pathology, and that clinicians should remember that load tolerance and soft tissue healing are individual factors with wide variability. That being said, they have provided an excellent and simple framework for us to work with.

They also emphasize the need for more research on early-stage tendon pathology, the area that is currently most lacking.

Study Strengths / Weaknesses:

This paper presented a pathology model for load-induced tendinopathy. The authors adequately reviewed existing literature and appropriately addressed potential shortcomings of their model.

Additional References:

  1. Khan KM, Cook JL, Bonar F, Harcourt PAM. Histopathology of common tendinopathies. Update and implications for clinical management. Sports Med 1999: 27: 393–408.
  2. Khan KM, Cook JL, Kannus P, Maffulli N, Bondesteam S. Time to abandon the ‘‘tendinitis’’ myth (editorial). BMJ 2002: 324: 626–627.
  3. Kraushaar B, Nirishi R. Tendinosis of the elbow (tennis elbow). Clinical features and findings of histological, immunohistochemical, and electron microscopic studies. J Bone Joint Surg Am 1999; 81-A: 259-278.
  4. Samiric T, Llic ZM, Handley CJ. Characterization of proteoglycans and their catabolic products in tendons and explants cultures of tendon. Matrix Biol 2004; 23: 127-140.
  5. Fredberg U, Bolvig L. Significance of ultrasonography detected asymptomatic tendinosis in the patellar and Achilles tendons of elite soccer players: a longitudinal study. Am J Sports Med 2002; 30: 488-491.
  6. Ferry ST et al. The effects of common anti-inflammatory drugs on the healing rat patellar tendon. Am J Sports Med 2007; 35: 1326-1333.
  7. Anitua E et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production in human tendon cells in culture. J Orthop Res 2005; 23: 281-286.
  8. Fredberg U, Stengaard-Pedersen K. Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation. Scand J Med Sci Sports 2008: 18: 3–15.