Tendinopathy

Disease/ Disorder

Definition

Persistent tendon pain and loss of function related to mechanical loading¹.  May be acute but is typically a chronic overuse and degenerative condition, exacerbated by mechanical loading. Encompasses tendinitis, tendinosis, paratenonitis, and tendon ruptures². Tendinitis typically refers to acute tendon related pain, as there is only a low-grade inflammatory response seen with tendinopathy. Tendinosis refers to chronic, degenerative tendinopathy. Paratenonitis refers to inflammation of the areolar tissue surrounding the tendon².

Etiology

• Overuse with poor or altered mechanics. Contributing factors include an altered healing response, relative ischemia, apoptosis of tenocytes and changes in neuronal homeostasis leading to stimulation of nerve endings and mast cells which alters the tendon matrix². Repeated mechanical stress and recurrent injuries with an absent or blunted inflammatory process may lead to the development of angiofibroblastic hyperplasia (fibroblasts and vascular granulation tissue).³

Epidemiology including risk factors and primary prevention

• The pathology is extremely common; incidence depends on the affected area, most often occurring in 30- to 60-year-olds.
  • Prevalence increases with age and is higher in women compared to men.⁴
• The most common upper extremity tendinopathies occur at the shoulder (ie, supraspinatus) and the common flexors and extensors of the elbow.
• At the lower extremity, the most common tendinopathies occur at the heel (ie, plantar fascia and Achilles tendon), greater trochanter (ie, gluteus medius and minimus), knee (ie, patellar tendon) and ankle (ie, tibialis posterior tendon).
• Risk factors may be divided into intrinsic (related to tendon or patient characteristics) and extrinsic (environmental or biomechanical) factors.⁴
  • Intrinsic risk factors:       
    • Medical and metabolic disorders (diabetes mellitus, obesity, hyperlipidemia, seronegative spondyloarthropathies)
    • Inflammatory conditions
    • Family history
    • Age
    • Limited or excessive joint mobility
    • Muscle weakness or deficits in neuromuscular control
    • Altered tendon structure.  
    • Polymorphisms in genes: collagen, type V, alpha 1 (COL5A1), tenascin C (TNC), matrix metalloproteinase-3 (MMP3), and estrogen-related receptor alpha (ESRRA) show highest association with tendon injury (ie, tendinopathy or rupture).
  • Extrinsic risk factors:
    • Overuse
    • Sudden increase in activity frequency and/or intensity
    • New physical activities
    • Lack of adequate recovery
    • Repetitive movements
    • Poor ergonomics
    • Treatment plans using fluoroquinolone, excess corticosteroid use, and statins

Patho-anatomy/physiology

• Normally, tendon fiber bundles are composed of fascicles consisting of tropocollagen (triple helix polypeptide chain) and blood vessels arranged parallel to the fascicles. The portion of the tendon that bears stress during mechanical loading is composed of three main components: Type 1 collagen, cells (mainly fibroblasts) and a non-collagenous matrix³
• Pathologic changes include macrostructural thickening and increased vascularity. Microstructure changes include degeneration and disorganization of collagen fibers, increased cellularity, minimal inflammation, lengthening and decreasing volume of tenocytes and increased Type III collagen density.⁴ The build-up of mucopolysaccharide in fibrous tendon sheath leads to mucoid (ie, myxoid) degeneration. This cycle repeats, leaving globular degeneration and the production of matrix metalloproteinases (MMPs)⁵, tenocyte apoptosis, chondroid metaplasia of the tendon and expression of protective factors such as insulin-like growth factor 1 (IGF-1) and nitric oxide synthetase (NOS) causing recurrent and chronic pain.⁶ In addition, there is increased COX-2 and IL-6 expression indicating a low grade inflammatory response.
• Upregulation of proteins, such as B-cell lymphoma interacting protein 3(BNIP3), implicated in pro-apoptotic pathways that promote oxidative injury may play a role in promoting tendinopathy³.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

• New onset/acute phase could begin as tendinitis with inflammation of the tendon or paratenon, followed by a blunted inflammatory process. Onset may be acute, traumatic, or insidious, presenting as an acute tear, often related to unaccustomed activity or a single instance of exertion. The healing process may be altered due to relative ischemic or other factors.
• The subacute or chronic nature of tendinopathy repeats the blunted inflammatory cycle resulting in a thickened and degenerated tendon that is more prone to pain or an acute tear.⁴
• Recovery from tendinopathy can take up to 6-12 months or longer; however, shorter recovery times can be found in those with less severe symptoms and tendon structural changes.⁴)

Specific secondary or associated conditions and complications

• The variant of calcific tendinosis (ie, calcific tendinitis) is a hydroxyapatite crystalline deposition into tendon, often affecting specific tendons such as the supraspinatus (Figures 1 and 2) and progresses through stages including fibrocartilage ingrowth, calcium formation, resorption and healing. Calcific tendinopathy is most painful during the resorptive phase and improves during tendon healing.
• Fatty infiltration can occur as the degenerated tendon vacuolizes and space is filled presumably with the proliferation of the areolar tissue in the adjacent paratenon.
• Tendon rupture can be a complication of rapid and/or forceful eccentric strain in the setting of advanced tendinopathy. Rupture can sometimes be the initial event signaling the presence of tendinopathy (e.g. Achilles tendon). Corticosteroid injections, particularly intra-tendinous may predispose a tendon to rupture.

Essentials of Assessment

History

• Symptoms are often described as a dull, aching, at times sharp pain. Soreness and stiffness are often reported in the morning, or after being still for long periods⁴. Usually pain is focal, non-radiating, improves with rest or ice, may improve with nonsteroidal anti-inflammatory drugs (NSAIDs), and worsens with use of the affected area.
• Patients with early initial symptoms may note temporary resolution of symptoms after warming-up the affected joint.
• Important historical points include prior injury of the affected limb, repetitive use, systemic illnesses, and recent medications including fluoroquinolones.
• Other presentations could include a history of an acute rupture (due to underlying tendinopathy), or complaints of an intermittent or chronic snapping tendon.
• In patients with progressed tendinopathy, pain may be constantly debilitating during activities.

Physical examination

• Inspection is often normal but can reveal fullness or focal thickening over superficial tendons. Observing postural alignment activities, and biomechanics are important to identify predisposing factors. Swelling may be localized at the area of tenderness.
• Palpation reveals tenderness anywhere from the enthesis to the myotendinous junction. Adjacent soft tissues or bursae may also be tender.
• Range of motion, active and passive, may be decreased or elicit end-range pain (e.g. elbow extension lag in severe lateral epicondylitis).
• Neurologic exam should be thorough and normal. Strength deficits, if present, should be pain-limited only.
• Special tests that can reproduce pain include passive stretching of affected tendon or resisted active motion of the tendon.

Functional assessment

• Evaluate for functional activities and ROM of adjacent and nearby joints. It is important to evaluate at least one joint above and below the lesion.
• Evaluate the posture, form, biomechanics, repetitive motions or other issues that may promote a recurrence or worsening in athletes or workers. Workplace or ergonomic evaluation may also be helpful.
• Fully evaluate the kinetic chain for range of motion (ROM) deficits, strength, alignment, mechanical and functional issues.
• Evaluate for pain during certain movements through pain-provoking tests.
  • Single leg calf-raises hopping for Achilles tendinopathy.
  • Single leg squats for patellar tendinopathy
  • Resisted extension of the wrist, index, or middle finger or gripping an object for elbow tendinopathy.

Laboratory studies

• May be necessary when multiple sites of tendon pain are identified to look for inflammation. Evaluate for conditions such as rheumatoid arthritis or collagen vascular diseases.
  • Association of positive Human Leucocyte Antigen (HLA)-B27 with bilateral Achilles tendinopathy.

Imaging

• Imaging is not necessary for tendinopathy clinical diagnosis¹.
• Radiographs may help determine the presence of intra-tendinous calcifications, calcified tendon insertions (enthesophytes), or concomitant articular or bone pathology such as fracture or apophysitis.
• Magnetic resonance imaging (MRI) is generally not indicated unless grading a tear is necessary for more advanced treatment, or evaluation of adjacent structures.
• Musculoskeletal ultrasound is an efficient, noninvasive, and relatively low-cost dynamic imaging modality for tendinopathy⁷. There are a variety of findings on ultrasound for identifying degenerative tendon changes of, which includes bone irregularities, calcific deposit (calcific tendinopathy), thickening, relative hypoechogenicity, swelling, tears of affected tendon and neovascularization.

Supplemental assessment tools

Differential diagnosis

1. Local inflammatory causes such as bursitis, synovitis, or apophysitis. The incidence of primary bursitis is disputed, but studies suggest true bursal distension is uncommon and unlikely to occur in the absence of gluteus medius tendon pathology⁸.
2. Local degenerative causes such as arthropathy, cartilage injury, muscle/tendon tears, or other intra-articular pathology.
3. Tumors, infection or vascular causes.
4. Referred or radicular pain.

Early predictions of outcomes

Functional outcome measures, some joint specific, can be utilized to chart the success, or lack thereof, of treatment⁹.Instruments to measure strength distal to the affected tendon over time can demonstrate treatment effects.

Environmental

Occupational settings that include forceful activities with high force and/or repetition, such as food industry workers, construction workers, and assembly line packers, increase risk for developing tendinopathy.⁴

Social role and social support system

• Persons with tendon pain may suffer depression or other mood disorders if they cannot participate in vocational or avocational activities. In such cases, activity adaptations or appropriate multidisciplinary treatment is required.
• Addressing psychosocial conditions that may precipitate into (or are implicated in) patient depression and anxiety may improve outcomes in patients with tendinopathy since these psychological conditions correlate with pain.⁴

Professional Issues

Patients with chronic recalcitrant tendinopathy may seek out unproven treatments, as acupuncture, magnets and other alternative medicine or “naturopathic” treatments, and should be counseled appropriately, on treatments that have scientific validity.

Rehabilitation Management and Treatments

Available or current treatment guidelines

The aim of conservative management revolves around initially decreasing tendon load, followed by progressive loading. At different disease stages

New onset/acute tendinopathy

1. Initial treatment should be tailored to the patient’s needs or desire to return to activity, symptom relief, the chronicity severity of tendinopathy, and the frequency of recurrence.
2. Progressive individualized strengthening that incorporates load and exercise progression for longer than 12 weeks should be prescribed as first-line treatment when treating tendinopathy⁴.
3. Acute exacerbations may be managed with relative rest, NSAIDs, and physical modalities, including ice.
4. Other modalities such as iontophoresis, phonophoresis, ultrasound, low-level laser therapy, shock wave therapy, and electrical stimulation have limited, if any, utility¹⁰.
5. Topical treatments including aspirin or diclofenac cream may be helpful and have a small amount of systemic absorption. Glyceryl trinitrate patch may decrease pain and enhance healing¹⁰.
6. Tendon sheath corticosteroid injections could give temporary partial pain relief, though their use is controversial. Intra-tendinous injections are not recommended, as they may result in tendon tears.
7. Corticosteroid injection of the rotator cuff decrease cell proliferation, alter collagen and extracellular matrix composition, impede inflammatory pathways, decrease cell viability, and increase apoptosis. These effects have been shown in-vitro as early as 24hrs after injection and lasting as long as 2-3 weeks. The evidence supports limiting a body part to 3 corticosteroid injections per year and waiting at least 1 month after injection before arthroscopic rotator cuff repair thereby allowing the tendon to reestablish its biomechanical properties Tendons exposed to steroids had a decreased load to failure and decreased strength in the early post-injection period.¹¹
8. Physical therapy could also include transverse friction massage, correcting biomechanics, ergonomic adjustments, and therapeutic exercises.
9. Isometric & eccentric exercise, patellar strapping and taping, dry needling (DN), and some injections have a short-term pain reducing effect in addition to functional improvements.¹²

Subacute/chronic

1. Strategies for secondary prevention and recurrence management could include early recognition of recurrent pain due to tendinopathy and enrollment in a program of eccentric training and symptomatic management as described above. Tendinopathy is commonly recognized in the subacute or chronic stage.
2. More advanced treatments include prolotherapy, sclerotherapy for neovascularization, percutaneous tenotomy, extracorporeal shockwave therapy, tendon hydrodissection and surgery.
3. Rehabilitation strategies could include preserving adjacent joint range of motion, improving flexibility or kinetic chain deficits and optimizing function in order to return to activity.
4. An alternative strategy for patients recalcitrant to conservative care is to palliate symptoms during times of exacerbation and optimize prevention strategies as discussed above.
5. An eccentric strengthening program has been demonstrated as potentially curative for Achilles tendinopathy. Active treatment such as calf-muscle exercise therapy is more effective than wait-and-see treatment.¹³
6. Patient education, activity modification, and regaining tendon length to enable normal wrist extensor dynamics promotes long-term function and pain improvements for lateral epicondylitis.^14-15
7. Eccentric exercise, dry needling, and autologous blood and saline injections were shown to be effective for long term pain relief and functional improvement in patellar tendinopathy.¹²

Prevention

Primary prevention for tendinopathy may include introducing specific exercise regimens that improve strength and coordination of muscle tendon units that may be predisposed to overuse or other usage-related tendinopathy.^{4, 16,17}

Coordination of care

• Coordinated and interdisciplinary: Patients with recalcitrant tendinopathy causing sustained disability due to pain and secondary weakness will require a coordinated interdisciplinary treatment approach.
• Integrated: Physical and occupational therapy, vocational counseling and rehabilitation psychologists can all play a role in treatment.
• Multidisciplinary: In cases of tendon tear or rupture a surgical consultation or debridement/repair of severe tendinopathy may be needed.

Patient & family education

• Family and societal roles may change due to disabling conditions.
• Often important to recovery in chronic cases is helping patients reestablish their role in the family through active rehabilitation exercises.
• Patient should be reassured that pain is allowed during and after performing exercises since sufficient tendon loading is necessary to cause meaningful clinical change⁴.

Emerging/unique Interventions

Impairment-based measurement

Patients with work limitations may require functional capacity evaluations to quantify their work tolerance and provide objective work modification recommendations.

Measurement of patient outcomes

Joint specific functional outcome measures, when needed⁹

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Physicians may learn and integrate into their practice newer techniques described to treat tendinopathy, including biologics (platelet-rich plasma (PRP)¹⁹, autologous blood, stem cells and other products).

Cutting Edge/ Emerging and Unique Concepts and Practice

• Injections under ultrasound and fluoroscopic guidance (Figure 3) increases accuracy. Guidance improves the accuracy of diagnostic injections. Ultrasound provides superior visualization of soft tissue structures, as tendons, without ionizing radiation.
• Injection of biologics including PRP, autologous blood ¹⁰ and stem cells offer alternatives to those who have failed conservative care.¹⁹
• Peritendinous hydrodissection may play a role in treating tendinopathies with neovascularity in adjacent fat pads.²⁰
• Extracorporeal shockwave therapy (ESWT) has demonstrated marginal or no significant symptom or functional improvements compared to placebo and other interventions such as PRP.¹²

Emerging/unique interventions

• Interventions directed at restoring normal tendon anatomy such as PRP, amniotic growth factor injections, and stem cell therapy are emerging treatments. PRP can be applied with or without tenotomy.
• PRP therapy is particularly promising for treating lateral epicondylitis; PRP therapy done independently is more effective than surgery for treating lateral epicondylitis.¹⁶
• PRP injections has been shown to have superior long-term benefits on patient outcomes in patellar tendinopathy and are appropriate in complex cases in combination with a rehabilitation program.¹⁹
• Scaffolds can be used to provide mechanical support for tendon extracellular matrix remodeling, or as carriers of deliverable factors that promote a suitable environment for native tissue regeneration.²¹

Nanotechnology may be used to create nanoparticles that label tendon stem cells and serve as carriers for gene therapy and drug delivery that promote responses at the cellular and extracellular level.²²

Gaps in the Evidence- Based Knowledge

• Injection of corticosteroid under imaging guidance has not been sufficiently studied to show increased efficacy.
• Controlled studies are required to establish the efficacy of injecting biologics including PRP and stem cells or tenotomy alone vs tenotomy and PRP.
• Participant characteristics are poorly reported in exercise trials in tendinopathy. The current exercise recommendations for tendinopathy treatment may lack external validity and reduce applicability to different patient populations.²³
• The most appropriate dosing, volume, and protocol for deploying PRP are not well defined. Many of the studies used different protocols and contained different levels of growth factors. This is of importance since many of the growth factors of interest are known to be short-lived.¹⁹

References

1. Scott, A. et al. ICON 2019: International Scientific Tendinopathy Symposium consensus: clinical terminology. Br. J. Sports Med 2020; 54: 260–262
2. Raney EB, Thankam FG, Dilisio MF, Agrawal DK. Pain and the pathogenesis of biceps tendinopathy. Am J Transl Res. 2017;9(6):2668-2683.
3. Scott, A, Backman LJ, Speed C. Tendinopathy: update on pathophysiology. J Ortho Sports Phys Ther 2015: 45(11): 833-841.
4.  Millar, N.L., Silbernagel, K.G., Thorborg, K. et al. Tendinopathy. Nat Rev Dis Primers 2021: 7: 10.
5. Jones GC, Corps AN, Pennington CJ, Clark IM, et al. Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human Achilles tendon. Arthritis Rheum. 2006; 54:832-842.
6.  Szomor ZL, Appleyard RC, Murrell GA. Overexpression of nitric oxide synthases in tendon overuse. J Orthop Res. 2006; 24:80-86.
7.  Vincenzo Ricci V, MD, Allison Schroeder A, MD, and Levent Özçakar L. Ultrasound Imaging for Lateral Elbow Pain: Pinpointing the Epicondylosis. Am J Phys Med Rehabi. 2020; 99(6): 560-561.
8. Barratt PA, Brookes N, Newson A.  Conservative treatments for greater trochanteric pain syndrome: a systematic review. British Journal of Sports Medicine. 2017; 51(2): 97–104.
9. Newcomer K. Martínez-Silvestrini JA. Gay R. White K. A Comparison of the Patient-Rated Forearm Questionnaire with Other Outcome Measurement Tools for Lateral Epicondylitis. Journal of Hand Therapy 2005; 18(4):400-405.
10. de Vos RJ, Weir A, Cobben LP, Tol JL. Tol The value of power Doppler ultrasonography in Achilles tendinopathy: a prospective study. Am J Sports Med. 2007; 35(10): 1696–1701.
11. Puzzitiello RN, Patel BH, Forlenza EM, et al. Adverse Impact of Corticosteroids on Rotator Cuff Tendon Health and Repair: A Systematic Review of Basic Science Studies. Arthroscopy, Sports Medicine, and Rehabilitation 2020; 2(2): e161–e169.
12. Vander Doelen, T, Jelley,. Non-surgical treatment of patellar tendinopathy: A systematic review of randomized controlled trials. J Sci Med Sports 2020; 23(2): 118–124.
13. van der Vlist AC, Winters M, Weir A, et al. Which treatment is most effective for patients with Achilles tendinopathy? A living systematic review with network meta-analysis of 29 randomised controlled trials. Br J Sports Med. 2021;55(5):249-256.
14.  Martínez-Silvestrini JA. Newcomer K. Gay R. White K. A clinical trial of concentric and eccentric strengthening for chronic lateral epicondylitis. Journal of Hand Therapy. 2005; 18(4):411-419.
15. McQueen KS, Powell RK, Keener T, Whalley R, Calfee RP. Role of strengthening during nonoperative treatment of lateral epicondyle tendinopathy. Journal of Hand Therapy. In Press.
16. Harøy, J. et al. The Adductor Strengthening Programme prevents groin problems among male football players: a cluster-randomised controlled trial. Br. J. Sports Med. 2019; 53: 150–157.
17. Andersson, S. H. et al. Preventing overuse shoulder injuries among throwing athletes: a cluster-randomised controlled trial in 660 elite handball players. Br. J. Sports Med. 2017; 51: 1073–1080 (2017).
18. Lenoir H, Mares O, Carlier Y. Management of lateral epicondylitis. Orthopaedics & Traumatology: Surgery & Research. 2019;105(8):S241-S246.
19. Andriolo L, Altamura SA,, Reale D, et al.,. Nonsurgical Treatments of Patellar Tendinopathy: Multiple Injections of Platelet-Rich Plasma Are a Suitable Option: A Systematic Review and Meta-analysis.  Am J Sports Med 2019; 47(4): 1001–1018.
20. Hall MM, Rajasekaran S. Ultrasound-Guided Scraping for Chronic Patellar Tendinopathy: A Case Presentation. PM&R. 2016; 8(6):593-596.
21. Gonzalez-Quevedo, D., Martinez-Medina, I., Campos, A., et al. Tissue engineering strategies for the treatment of tendon injuries: a systematic review and meta-analysis of animal models. Bone Joint Res 2018; 7: 318–324 (2018).
22. Parchi, P. D. et al. Nanoparticles for tendon healing and regeneration: literature review. Front. Aging Neurosci. 2016; 8: 202.
23. Auliffe SM, Korakakis V, Hilfiker R, et al. Participant characteristics are poorly reported in exercise trials in tendinopathy: A systematic review. Phys Ther Sport. 2021; 48:43-53.

Original Version of the Topic

Chris Visco, MD. Tendinopathy. 4/5/2013

Previous Revision(s) of the Topic

Julio Martinez-Silvestrini, MD and Hans Knopp, MD. Tendinopathy. 4/4/2017

Author Disclosures

Julio Martinez-Silvestrini, MD, CAQSM
Nothing to Disclose

Alvaro Nava, BSPH, MS
Nothing to Disclose

Christopher Elmore, MD
Nothing to Disclose