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Tendinopathy and idiopathic osteoarthritis (OA) are prevalent in middle-aged active individuals and represent a significant disease burden. Both disorders are associated with overloading of musculoskeletal tissues and both respond well to mechanotherapy. Other shared risk factors include genetic predisposition, obesity and specific age.1 ,2 Both disorders have a multifactorial pathogenesis.
Tendon and cartilage both consist of an extracellular matrix with mainly collagen (type I and II respectively), proteoglycans and sparse distribution of specialised cells. The key histopathological feature of tendinopathy and OA is extracellular matrix degeneration. The 2015 study on tendon structural changes in patients with diabetes in BJSM by de Jonge et al 3 points to similarities between tendinopathy and OA, which we frequently notice in our collaborative tendon and OA research group. These similarities between degenerative tendinopathy and OA may have clinical implications. Below, we would like to display some examples.
Can knowledge about tendons help us better understand OA or vice versa?
Role of advanced glycation end products
Advanced glycation end products (AGEs) accumulate in connective tissues of patients with type 2 diabetes. De Jonge et al 3 showed more tendon structure disorganisation in individuals with type 2 diabetes compared to controls. AGEs form collagen cross-links and increase the stiffness of the collagen network.3 However, disorganised tendon structure was not associated with an increased estimated level of AGE accumulation.3 It remains therefore unknown which mechanism is responsible for the disorganised tendon structure in diabetes. A key to answer this question might be provided from recent preclinical OA research. AGEs enhance proinflammatory cytokine production and limit collagen type II production in human OA chondrocytes.4 Consequently, AGEs are possibly not directly responsible for mechanically induced degeneration, but indirectly as a result of altered matrix turnover. This mechanism can make individuals with diabetes more prone to both OA and tendinopathy and can cause impaired rehabilitation.
Inflammation: a continuing debate
Patients with diabetes, as included in the study of de Jonge et al 3 are known to have higher levels of inflammatory mediators.1 Since classic inflammatory cells were not found in large numbers in chronic tendinopathic tissue specimens, the designation ‘tendinitis’ has been abandoned.5 While OA is also characterised by matrix degeneration, the ‘–itis’ terminology has been maintained and recently the role of inflammatory cytokines has gained more attention. Locally produced proinflammatory cytokines–such as interleukin (IL)-1β, IL-6 and tumour necrosis factor α—result in cartilage destruction and pain in patients with OA.1 Recent studies demonstrate immune cells in biopsies of chronic tendinopathy patients, but studies on cytokines are sparse. The OA studies implicate that inflammatory cytokines may also mediate degenerative tendinopathy at certain stages.
Structural tissue changes and symptoms
De Jonge et al 3 focused on tendon structural changes in patients with diabetes and demonstrated more tendon structure disorganisation. In tendinopathy and OA, the degree of structural changes—measured with ultrasound in Achilles tendinopathy and with X-ray in knee OA—is only weakly associated with patient-reported pain.6 Nonetheless, the Food and Drug Administration approved radiographic joint space narrowing as outcome for disease-modifying treatment in OA. Improving this parameter with regenerative strategies is a current challenge in OA research, but tendon structure can improve to normal values with conservative treatments in patients with Achilles tendinopathy. Normalisation of tendon structure, however, is not associated with decreased symptoms in the short term.6 It is therefore questionable whether treatments aiming to restore cartilage structure should be expected to decreased symptoms in short-term studies. More knowledge about the relation between structural tissue changes and symptoms on short but also on long term will help designing better treatments for patients. Conventional imaging parameters are currently no strong predictors of symptom progression in OA and tendinopathy, and therefore less valuable for clinicians.
Neuropeptides—undesirable or necessary?
Musculoskeletal pain is associated with peripheral neuronal alterations that influence nociception.7 ,8 Knee OA is associated with an upregulation of intra-articular neuropeptides–such as nerve growth factor (NGF). Anti-NGF injections reduced pain in the first clinical OA studies. Recent tendon studies, however, suggest that the nervous system does not only play a role in pain generation, but also in tissue repair through efferent pathways.7 Preclinical tendon studies indicate that balanced neuropeptide levels are critical for repair of acute tendon lesions.7 Disturbed neuropeptide levels also contribute to degenerative proliferation and transformation of tenocytes. Straightforward blocking of neuropeptides, as performed with biologicals in clinical OA studies, may be too simplistic.7 Harmonising the inhibition of neuropeptide-mediated pain and stimulation of neuropeptide-mediated tissue repair might be a key for success in both tendinopathy and OA treatment.
A chance to kill two birds with one stone
We would like to emphasise that tendinopathy and OA should not be regarded as identical diseases—there are also differences. We acknowledge that cartilage and tendon tissues have different mechanical functions and are surrounded by other structures that can—directly or indirectly—influence treatment outcomes. The work by de Jonge et al 3 highlights the complex pathophysiology of tendinopathy and triggers a broader debate on common principles between musculoskeletal disorders. The aforementioned examples demonstrate several similarities between tendinopathy and OA. It can help clinicians to account effects of comorbidities on these musculoskeletal diseases and to consider new treatment options that shows potential in one of both conditions.
Contributors R-JdV prepared the first draft of the paper. GJVMvO, SMAB-Z and JANV revised the paper.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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