Born to run: The paradox of biomechanical force in spondyloarthritis from an evolutionary perspective

Debusschere, Karlijn; Cambré, Isabelle; Gracey, Eric; Elewaut, Dirk

doi:10.1016/j.berh.2018.07.011

Cited by 21 publications

(14 citation statements)

References 56 publications

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“…An interesting hallmark of these structures is that they have to withstand high exposure to biomechanical stresses. This suggests that biomechanical stress could impact the clinical features of these diseases 4. In support thereof, recent clinical data suggest that highly demanding physical labour is linked to more severe structural progression in ankylosing spondylitis (AS)5 and PsA 5–9.…”

Section: Introductionmentioning

confidence: 99%

Running promotes chronicity of arthritis by local modulation of complement activators and impairing T regulatory feedback loops

et al. 2019

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ObjectivesThe mechanisms driving onset of joint inflammation in arthritides such as rheumatoid arthritis and spondyloarthritis and the conversion to disease chronicity are poorly understood. We hypothesised mechanostrain could play an instrumental role herein by engaging local and/or systemic pathways, thereby attenuating disease course and outcome.MethodsThe development of collagen antibody-induced arthritis (CAIA) in C57BL/6 mice was evaluated both clinically and histologically under different loading regimens: control, voluntary running or hindpaw unloading. Bone surface porosity was quantified by high-resolution µ-CT. Gene expression analyses were conducted by microarrays and qPCR on microdissected entheses, murine and human synovial tissues (both normal and inflamed). Serum cytokines and chemokines were measured by ELISA. The influence of complement activation and T regulatory (Treg) cell function on the induction and resolution phase of disease was studied by respectively pharmacological modulation and conditional Treg depletion.ResultsVoluntary running strongly impacts the course of arthritis by impairing the resolution phase of CAIA, leading to more persistent inflammation and bone surface porosity. Mechanical strain induced local complement activation, increased danger-associated molecular pattern expression, activating Fcγ receptors as well as changes in fibroblast phenotype. Interestingly, complement C5a receptor blockade inhibited the enhanced joint pathology caused by voluntary running. Moreover, Treg depletion led to a loss of disease resolution in CAIA mice, which was not observed under voluntary running conditions.ConclusionsRunning promotes onset and chronicity of arthritis by local upregulation of complement activators and hampering regulatory T cell feedback loops.

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Section: Introductionmentioning

confidence: 99%

Running promotes chronicity of arthritis by local modulation of complement activators and impairing T regulatory feedback loops

et al. 2019

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“…In PsA, as in other forms of spondyloarthritis, enthesitis can occur in both the upper and lower extremities, but the latter seems to be more frequently involved-particularly the heel (13,14). Reasons for the higher prevalence of enthesitis in lower extremities are unknown, although some studies have suggested that this may be due to the anatomy and mechanical load at these sites (15,16). In a prospective, longitudinal cohort of Canadian patients with PsA, most patients had enthesitis involvement in the greater trochanter and Achilles tendon as well as the lateral and medial epicondyles, indicating that assessment of upper sites is also important when evaluating enthesitis (10).…”

Section: Introductionmentioning

confidence: 99%

Disease Characteristics, Quality of Life, and Work Productivity by Enthesitis Site: Real-world Data From the US Corrona Psoriatic Arthritis/Spondyloarthritis Registry

Mease

Liu²,

Rebello³

et al. 2020

J Rheumatol

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Objective To assess the impact of clinical enthesitis by body site in patients with psoriatic arthritis (PsA). Methods Adults with PsA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013–March 2018) were included. Enthesitis at enrollment was assessed via the Spondyloarthritis Research Consortium of Canada Enthesitis Index and classified by affected sites (upper, lower, or both). Disease activity (eg, Clinical Disease Activity Index, clinical Disease Activity Index for PsA), patient-reported outcomes (PROs; eg, patient-reported pain and fatigue), and work productivity were compared between those with and without enthesitis using t or Wilcoxon rank-sum tests for continuous variables and χ2 or Fisher exact tests for categorical variables. The association of enthesitis with disease activity and PRO measures vs no enthesitis was modeled using multivariable-adjusted linear or logistic regression. Results Of 2003 patients with PsA, 391 (19.5%) had enthesitis: 80 (20.5%) in upper sites only, 137 (35.0%) in lower sites only, and 174 (44.5%) in both. Regardless of location, disease activity and PROs were worse in patients with vs without enthesitis. In adjusted models, presence of enthesitis at any site was significantly associated with worse disease activity vs no enthesitis. Enthesitis in lower or both upper and lower sites was associated with higher pain and fatigue scores and greater work impairment vs no enthesitis. Conclusion Patients with clinical enthesitis had worse disease activity regardless of enthesitis location vs those without enthesitis, and patients with enthesitis in lower or both upper and lower sites had worse pain, fatigue, and work impairment.

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“…The overall beneficial effect of physical activity in clinical trials is mild and most outcome measurements available are potentially influenced by general well-being, but there were no harmful effects observed in SpA patients. In recent years there were no studies confirming the harm of insufficient mobilization, yet, at least a certain baseline of physical activity is necessary to maintain joint stability [47]. Conversely, multiple observational studies demonstrate excessive mechanical strain to be a likely trigger for disease activity and indicate potential differences between peripheral and axial loading (figure 1).…”

Section: Discussionmentioning

confidence: 99%

Spondyloarthritis on the Move: Biomechanical Benefits or Harm

Mechelen

Lories

2020

Curr Rheumatol Rep

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Purpose of review Physical activity is beneficial in several diseases including spondyloarthritis despite mechanical stress being suggested as a trigger of disease onset or activity. Moreover, there is no clear answer as to where physiological loading of the joints ends and pathological overloading begins.The aim of this review is to provide an overview of what is known about exercise and biomechanical loading in spondyloarthritis.Recent findings Recent studies focused on the impact of mechanical loading in healthy individuals and spondyloarthritis patients, demonstrating an overlap between the groups and pointing out possible beneficial and detrimental activities. The discovery that several animal models of inflammatory arthritis are dependent on mechanical stress helps unraveling the involved molecular pathways.Summary There is a knowledge gap between the beneficial effect of exercise reported in clinical trials and the harm seen in observational studies and animal models. Imaging studies provide a first step in joining these two opposites by highlighting a wide-ranging spectrum between healthy and diseased joints. Future research is warranted on specific interventions in well-defined patient populations and in animal models in order to understand the pathogenesis. Targeted exercise therapy and prevention should be considered specific goals.

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Born to run: The paradox of biomechanical force in spondyloarthritis from an evolutionary perspective

Cited by 21 publications

References 56 publications

Running promotes chronicity of arthritis by local modulation of complement activators and impairing T regulatory feedback loops

Running promotes chronicity of arthritis by local modulation of complement activators and impairing T regulatory feedback loops

Disease Characteristics, Quality of Life, and Work Productivity by Enthesitis Site: Real-world Data From the US Corrona Psoriatic Arthritis/Spondyloarthritis Registry

Spondyloarthritis on the Move: Biomechanical Benefits or Harm

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