The Current State of The Science of Tendinopathy
A revolution is in the making for the therapy and prediction of sports injuries. The next advances will likely come through genetics and genomic analysis. Functional genomics has led to a surge in research on the genomic characteristics of basic and clinical phenomena that can predict and alter the mechanisms of health and disease. Progress is being made on linking the genome with the metabolic characteristics of tissues and cells.(Beloqui 2009) Recent studies have hinted at the relationship between tendinopathy and genetics.
Genetics has even been found to play a role in motivation to exercise (Eisenmann and Wickel 2009) and can be responsible for a lack of response to exercise training. Specific genes have been associated with leisure time activity. (De Moor, Liu et al. 2009) Prediction is critical for groups as diverse as professional sports teams to the military. Susceptibility to injuries such as stress fractures and Achilles tendinopathy will alter training regimens as risk assessment and prevention strategies improve.
Genetics may play a specific role in the pathogenesis of many athletic injuries. Studies of Achilles tendinopathy suggest a genetic component. This was first hypothesized when a study revealed an apparent association of the O blood group and Achilles tendon injuries in the Hungarian and Finnish populations. Chromosome 9 was then thought to be the locus of a change to this gene or a closely linked gene. Other studies did not demonstrate this association. More recently genomic studies have shown that individuals with variants of the tenascin-C gene(Mokone, Gajjar et al. 2005) or alterations in the COL5A1 gene(Mokone, Schwellnus et al. 2006), especially a BstUI restriction fragment length polymorphism are more prone to develop Achilles tendinopathy. Future genomic research is likely to yield much more information about susceptibility to injury.
In this article we’ll examine the current state of the science of tendinopathy and update periodically as new research blossoms.
|“... future genomic research is likely to yield much information about optimal treatment and also about the susceptability to injury..."
The Rise of Tendinopathy
Healthy tendons are white, firm, have a fibroelastic texture and are able to handle heavy loads. Shapes of tendons vary from short and broad, such as the quadriceps tendon, to long and rounded, such as the peroneal tendons. Tendons transfer the forces generated by muscles to bone. This force transfer results in movement. The elasticity of tendons allow for improved muscle function through the force-length-tension relationship. This improved function also result from the ability of the tendon to store mechanical potential strain energy. The storage and recovery of energy is a passive process that does not need to be turned on and off. In fact, the mechanical properties of tendon are not dependent upon metabolic activity.
The tensile strength of tendon at 5.0 kN/cm2 to 10 kN/cm2 is higher than that of bone. With the strength of tendons at times exceeding the strength of bone, injuries such as fifth metatarsal styloid process avulsion fractures may occur. Tendons may become injured when repeated loads exceed their strength capacity. The elastic modulus of an injured tendon is lessened while its stiffness is increased.
The structures which surround tendons consist of five types of tissue(Jozsa 1997):
- Fibrous sheaths – These are channels through which usually longer tendons glide. Friction is reduced through their course. The grooves and notches through which tendons must pass are almost always lined with fibrocartilage just below the fibrous sheath. Overlying the notches and channels, above the tendons, are often retinaculum such as the superior and inferior extensor retinacula at the ankle and the superior and inferior peroneal retinacula.
- Reflection pulleys – The cuboid groove is an example of a reflection pulley. Reflection pulleys are areas in which the tendon must make a dramatic change in direction.
- Synovial sheaths - Where friction may occur, tendons are often covered with synovial sheaths which usually secrete a friction reducing peritendinous fluid.
- Peritendinous sheaths – Tendons such as the Achilles tendon, which do not have a true synovial sheath may be covered with tissue that serves a similar function.
- Tendon bursa – The tendon bursae reduce friction. The retrocalcaneal bursa and pes anserinus bursa are well known examples.
Tendinitis, The Term That Needs To Die
Tendinopathy is now the term of choice for the clinical condition following overuse injury. The terms tendinosis and tendinitis are histopathological descriptions and should not be used without microscopic confirmation. Overuse tendon injuries cause pain, reduce strength and function, and decrease tolerance and length of exercise. The Achilles tendon and posterior tibial tendon are among the most common areas affected by tendinopathy in runners.
Surgical specimens taken from patients with well-established tendinopathy show little to no signs of inflammation. Instead, the specimens show hypercellularity, an increase in proteoglycan content, vascularization, and a loss of the usual tightly bundled collagen appearance. Tendinopathic tissue is usually grey or brown in color. Physically the tissue is soft and fragile. Animal preparations do not demonstrate inflammation as a component of long standing tendon injury. Inflammation is only seen in cases of acute and extreme tendon loading. The microscopic pathology of both mid-tendon and enthesis injuries is histologically similar. Repetitive overload and microtrauma can occur in conjunction with non-uniform stress within a tendon. The result is local fiber degeneration. A single abnormal loading cycle (e.g. a misstep) could be enough to create isolated fibril damage. The patient would not likely recall a specific injury. Neer believed impingement could be a cause of tendinopathy in the supraspinatus tendon below the anterior margin of the acromium. (Neer 1983) An analogous process may contribute to peroneus longus tendinopathy adjacent to the cuboid bone.
Tendon overload creates matrix changes in the collagen structure. There is an increase in proteoglycans, and cellular protein and enzyme production is altered. Production of prostaglandin E2 and leukotriene B4 are increased. These compounds likely contribute to the development of tendinopathy. Apoptosis may also play a role. An increase in cytochrome-c related caspace activation is a potential inductive pathway for apoptosis. Heat shock protein (HSP-25) is also found in animal models of tendinopathy with apoptosis. (Xu and Murrell 2008)
|“... tendinopathy is now the term of choice for the clinical injury to tendons that follows overuse injury..."
Theories of Tendon Pathology
We need to look at other possible mechanisms for overuse tendinopathy, as inflammation is no longer believed to be the major cause. The features described above are all compatible with the current major theories of tendinopathy. The theory of incomplete healing views the injured tendon as being in a healing phase, with active cellular activity and increased protein production occurring in the midst of a disorganized matrix and neovascularization. This has also been termed “failed healing”. (Iglehart 2006)
Overuse tendon injuries have also been viewed as a degenerative process. The terms hypoxic degeneration, mucoid degeneration or hyaline degeneration are often applied. This suggests an end stage and difficult to reverse process. (Jozsa and Kannus 1997) It is possible that a continuum may exist with incomplete healing leading ultimately to a degenerative process. Cook and Purdam have described this hypothesis. (Cook and Purdam 2009)
Magnetic resonance imaging (MRI) and diagnostic ultrasound (US) are the most frequently employed diagnostic procedures. In contrast to tenography, both of these procedures are non-invasive and cause no further to damage to the tissues. US is a fast and inexpensive technique which can be performed in an office setting. Tendon thickening, echogenic changes around the tendon, and adhesions are readily seen. Tendons affected by tendinosis, on US examination, show low reflectivity peripherally. In chronic tendinosis, peritendinous adhesions are seen as a hypoechoic paratenon with poorly defined borders. MRI using relatively small spaced images provide greater detail, but takes longer to perform and is considerably more expensive.
Clinical examination is still an important component of the evaluative process. Bains and Porter (2006) state that “clinical evaluation remains the main criterion measure” for evaluation of potential areas of tendinopathy. (Bains 2006)
Physical examination, MRI, and diagnostic ultrasound could be useful in the diagnosis of this clinical entity.Tenography may sometimes be an accurate indicator of injury, but is no longer widely used.
|“... inflammation is no longer believed to be the cause of most overuse tendon injury..."
We should all be transitioning to the concept of using the word tendinopathy as the general term for tendon injury. Tendonitis, as currently defined, is not seen in long standing tendon injuries. Tendinosis with the changes described is seen, but tendinopathy is the correct term. Further research should reveal patterns of susceptability to tendon injuries and ultimately provide evidence for the best methods of treatment.
Bains, S., Porter, K (2006). "Lower limb tendinopathy in athletes." Trauma 8: 213–224.
Beloqui, A., Guazzaroni, M., Pazos, F. , Vieites,J. (2009). "Reactome Array: Forging a Link Between Metabolome and Genome." Science 326(October 9): 252-257.
Coghlan, B. A. and N. M. Clarke (1993). "Traumatic rupture of the flexor hallucis longus tendon in a marathon runner." Am J Sports Med 21(4): 617-618.
Cook, J. L. and C. R. Purdam (2009). "Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy." Br J Sports Med 43(6): 409-416.
De Moor, M., Y. J. Liu, et al. (2009). "Genome-Wide Association Study of Exercise Behavior in Dutch and American Adults." Med Sci Sports Exerc.
Eisenmann, J. C. and E. E. Wickel (2009). "The biological basis of physical activity in children: revisited." Pediatr Exerc Sci 21(3): 257-272.
Hamilton, W. G. (2008). "Posterior ankle pain in dancers." Clin Sports Med 27(2): 263-277.
Iglehart, J. K. (2006). "The new era of medical imaging--progress and pitfalls." N Engl J Med 354(26): 2822-2828.
Jozsa, L. and P. Kannus (1997). "Histopathological findings in spontaneous tendon ruptures." Scand J Med Sci Sports 7(2): 113-118.
Jozsa, L., Kannus, P (1997). Human Tendons: Anatomy, Physiology, and Pathology, Human Kinetics.
Michelson, J. and L. Dunn (2005). "Tenosynovitis of the flexor hallucis longus: a clinical study of the spectrum of presentation and treatment." Foot Ankle Int 26(4): 291-303.
Mokone, G. G., M. Gajjar, et al. (2005). "The guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene is associated with achilles tendon injuries." Am J Sports Med 33(7): 1016-1021.
Mokone, G. G., M. P. Schwellnus, et al. (2006). "The COL5A1 gene and Achilles tendon pathology." Scand J Med Sci Sports 16(1): 19-26.
Neer, C. (1983). "Impingement lesions." Clin Orthop Relat Res 173: 70-77.
Oloff, L. M. and S. D. Schulhofer (1998). "Flexor hallucis longus dysfunction." J Foot Ankle Surg 37(2): 101-109.
Pribut, S. (2010). "Challenging Running Injuries." Podiatry Management Magazine January 2010.
Schulhofer, S. D. and L. M. Oloff (2002). "Flexor hallucis longus dysfunction: an overview." Clin Podiatr Med Surg 19(3): 411-418, vi.
Slater, H. K. (2007). "Acute peroneal tendon tears." Foot Ankle Clin 12(4): 659-674, vii.
Sobel M, P. H., Geppert MJ, Thompson FM, DiCarlo EF, Davis WH (1994). "Painful os peroneum syndrome: a spectrum of conditions responsible for plantar
lateral foot pain." Foot Ankle Int 15((3) March): 112-124.
Ting, A. Y., W. B. Morrison, et al. (2008). "MR imaging of midfoot injury." Magn Reson Imaging Clin N Am 16(1): 105-115, vi.
Xu, Y. and G. A. Murrell (2008). "The basic science of tendinopathy." Clin Orthop Relat Res 466(7): 1528-1538.