Tendinopathy: The New Science of Pain and Repair

This summary is based on the Nature Reviews Disease Primers article “Tendinopathy” by Neal L. Millar et al. (published in 2021). It outlines the current scientific understanding of the condition’s pathology, diagnosis, and management.

Overview

Tendinopathy is a complex, multifaceted clinical syndrome characterised by persistent pain, localised swelling, and impaired performance. It is a spectrum of changes that occur when a tendon fails to heal correctly following injury or repetitive strain. While often referred to in the past as “tendinitis” (implying inflammation) or “tendinosis” (implying degeneration), the term tendinopathy is now preferred to encompass the diverse histological and molecular changes involved.

1. Epidemiology and Risk Factors

The condition is highly prevalent, accounting for up to 30% of musculoskeletal consultations.

• Common Sites: The most frequently affected areas are the Achilles tendon, patellar tendon (jumper’s knee), rotator cuff, and the medial/lateral epicondyles (golfer’s/tennis elbow).
• Demographics: Prevalence increases with age. In sports, it affects up to 50% of elite runners (Achilles) and 40% of volleyball players (patellar).
• Risk Factors: These are divided into extrinsic (e.g. training errors, poor equipment, occupational repetitive loading) and intrinsic (e.g. age, genetics, obesity, metabolic conditions like diabetes and high cholesterol certain medications such as fluoroquinolones and excessive corticosteroid use).

2. Pathophysiology

Healthy tendons are composed of highly organised Type I collagen fibres. In tendinopathy, this structure undergoes significant “disrepair”:

• Matrix Disorganisation: Collagen fibres become fragmented and haphazard. There is a shift from Type I collagen to the weaker, less organised Type III collagen.
• Cellular Changes: Resident cells (tenocytes) change shape, and there is an increase in programmed cell death (apoptosis).
• Neovascularisation and Innervation: There is an abnormal “sprouting” of new blood vessels and sensory nerves into the tendon tissue. These new nerves are thought to be a primary source of the chronic pain experienced by patients.
• Inflammatory Role: While not a classic inflammatory disease (like rheumatoid arthritis), the Primer highlights that inflammatory mediators (cytokines and prostaglandins) play a critical role in the early and chronic stages of the disease.

3. Diagnosis

Diagnosis remains predominantly clinical, based on patient history and physical examination.

• Symptoms: Pain that is usually “load-dependent” (worsens with activity) and localized tenderness.
• Imaging: Ultrasound and MRI are frequently used to confirm the diagnosis and assess the extent of structural damage. However, the article notes a “clinico-radiological paradox”: many people have structural changes on scans but no pain, while others have severe pain with relatively “normal” looking tendons.

4. Management Strategies

Management is often challenging, with no “one-size-fits-all” cure. The primary goal is to increase the tendon’s load-bearing capacity.

• Exercise-Based Rehabilitation: This is the gold-standard treatment. Progressive loading (including isometric, isotonic, and heavy slow resistance training) is essential to stimulate tendon remodelling.
• Pharmacotherapy: NSAIDs may provide short-term pain relief but do not address the underlying pathology. Corticosteroid injections are common but are now used with caution due to the risk of long-term tendon weakening.
• Adjunct Therapies: Treatments like shockwave therapy (ESWT) and Platelet-Rich Plasma (PRP) injections show varied results and lack consistent high-level evidence.
• Surgery: Generally considered a last resort when 6–12 months of conservative management has failed.

5. Future Outlook

The Primer concludes that future research must move beyond viewing tendinopathy as simple “overuse”. There is a need for:

• Precision Medicine: Tailoring treatments based on an individual’s genetic and metabolic profile.
• Biological Therapies: Developing drugs that can specifically target the molecular pathways causing matrix degradation.
• Refined Rehabilitation: Better understanding of how much “load” is optimal for different stages of the disease to prevent the “cycle of disrepair.”

High Cholesterol Can Cause Tendon Pathology

A recent literature review by Yang et al. suggests that high blood cholesterol is a risk factor in the development and progression of tendon pathology. They found that cholesterol levels were directly correlated with the severity of tendon problems. There is evidence that elevated cholesterol levels lead to inflammatory, structural and mechanical changes in tendons which predispose patients with high cholesterol levels to an increased risk of developing tendinopathies.

High Cholesterol Linked To Tendon Problems

A group of Australian researchers have conducted a systematic review of literature to find articles that looked at the relationship between fat levels in blood and tendon pathology and/or pain. Their results were published in the British Journal of Sports Medicine. They found that people with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol (“bad cholesterol”) and triglycerides, as well as lower high-density lipoprotein cholesterol (“good cholesterol”).

The researchers conclude that although a relationship exists between an individual’s lipid profile and tendon health, further longitudinal studies are required to determine whether it is a cause and effect relationship.

Interestingly, the results of the China Study, one of the most comprehensive studies of nutrition ever conducted, found that one of the best predictors of diseases of affluence (heart disease, diabetes, cancer, etc.) was blood cholesterol.

Tender Tendons

Tendon problems can affect many areas of the body such as the elbows (tennis elbow and golfer’s elbow), hips, knees (runner’s knee), ankles (Achilles tendon) and feet (policeman’s heel). In the past these problems went by the name of tendonitis. The suffix “itis” was used because it was thought that inflammation was present. Imaging techniques like ultrasound and MRI scans have revealed that there is in fact very little inflammation (except possibly in the very early stages) but instead degenerative changes were found. This led to the replacement of tendonitis by tendinosis. The suffix “osis” means degeneration. Recently however, studies have found that the imaging findings are not directly related to symptoms:

• some people are symptom-free even though they have structural tendon pathology
• as symptoms improve, structural pathology doesn’t change
• structural pathology is not necessarily a good predictor of recovery

This has led to a yet another word being used…tendinopathy. The “pathy” simple means problem…something is wrong but we’re not exactly sure what it is! It’s thought that past experience, emotion and adverse pain beliefs could lead to a hypersensitive nervous system.

That being said, it’s believed that tendon overload plays a crucial role, whereby the rate of wear is greater than the rate of repair. Therefore, inciting factors tend to fall under 2 categories.

1) Factors that increase the rate of tear:

• repetitive impact activities
• tendon compression
• sudden increase in training volume, intensity or frequency
• muscle weakness
• faulty biomechanics
• obesity

2) Factors that decrease the rate of repair:

• menopause
• age
• rheumatoid arthritis
• type II diabetes
• high cholesterol
• statins
• smoking

After a thorough clinical assessment the probable causative factors should be addressed when possible. The aim of treatment is to decrease pain, promote healing and improve function. There are several different treatments that are used. The choice usually depends on the site, severity of symptoms and the stage of presentation. In the early stages when there is possibly some inflammation present, NSAIDs, rest, ice, wedges, taping or splinting can be used. Obviously, physiotherapy and acupuncture are useful and corticosteroid injections are helpful (especially when performed around the tendon rather than in it). Surgery is a last resort and results can sometimes be disappointing. Some of the best evidence is for the use of extracorporeal shock-wave therapy or a progressive exercise programme. In fact, a progressive exercise programme should be part of all treatment packages particularly alongside treatments that are successful at decreasing pain but that don’t improve healing or function. A graduated exercise programme can ensure the long-term success of treatment.