Exercise-induced pain changes associate with changes in muscle perfusion in knee osteoarthritis: exploratory outcome analyses of a randomised controlled trial

Elisabeth Bandak, Mikael Boesen, Henning Bliddal, Robert G C Riis, Sabrina Mai Nielsen, Louise Klokker, Cecilie Bartholdy, Janus Damm Nybing, Marius Henriksen, Elisabeth Bandak, Mikael Boesen, Henning Bliddal, Robert G C Riis, Sabrina Mai Nielsen, Louise Klokker, Cecilie Bartholdy, Janus Damm Nybing, Marius Henriksen

Abstract

Background: Exercise therapy is recommended for knee osteoarthritis (OA), but the underlying mechanisms of pain relief are not fully understood. The purpose of this study was to explore the effects of exercise on muscle perfusion assessed by dynamic contrast enhanced MRI (DCE-MRI) and its association with changes in pain in patients with knee OA.

Methods: Exploratory outcome analyses of a randomised controlled study with per-protocol analyses ( ClinicalTrials.gov : NCT01545258) performed at an outpatient clinic at a public hospital in Denmark. We compared 12 weeks of supervised exercise therapy 3 times per week (ET) with a no attention control group (CG). Analyses of covariance (ANCOVA) were used to assess group mean differences in changes from baseline to week 12 in knee muscle perfusion quantified by DCE-MRI, patient-reported pain and function using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, knee extensor and flexor muscle strength tests, and the six-minute walking test (6MWT). Spearman's correlation coefficients were used to determine the correlation between changes in DCE-MRI variables, KOOS, muscle strength, and 6MWT. The potential effect mediation of the DCE-MRI perfusion variables was investigated in a post-hoc mediation analysis.

Results: Of 60 participants randomised with knee osteoarthritis, 33 (ET, n = 16, CG, n = 17) adhered to the protocol and had complete DCE-MRI data. At follow-up, there were significant group differences in muscle perfusion changes and clinically relevant group differences in KOOS pain changes (10.7, 95% CI 3.3 to 18.1, P = 0.006) in favor of ET. There were no significant between-group differences on muscle strength and function. The changes in pain and muscle perfusion were significantly correlated (highest Spearman's rho = 0.42, P = 0.014). The mediation analyses were generally not statistically significant.

Conclusion: The pain-reducing effects of a 12-week exercise program are associated with changes in knee muscle perfusion quantified by DCE-MRI in individuals with knee OA, but whether the effects are mediated by muscle perfusion changes remains unclear.

Trial registration: ClinicalTrials.gov: NCT01545258 , first posted March 6, 2012.

Keywords: Exercise; Muscle perfusion; Osteoarthritis; Pain.

Conflict of interest statement

MB is chairman of the medical and scientific board, Image Analysis Ltd., London, UK and has stock options. He has received fees/honoraria (<$10,000) covering travel/accommodation costs as well as a small yearly honorarium. All other authors have nothing to declare.

RR and JDN: Consultants for Image Analysis Ltd. (analyses of MRIs and conventional radiographs).

Figures

Fig. 1
Fig. 1
DCE-MRI analysis. DCE-MRI analysis is based on changes in signal intensity over time for each voxel within the VOI. The signal intensity changes calculated relatively to the baseline signal intensity and the changes over time can be plotted as time-intensity-curves (TICs): a TIC from a point of interest in the popliteal artery with the characteristics of tissue with high perfusion: rapid increase in signal intensity, which reaches a plateau and a subsequent rapid decrease (washout) (x-axis: time (s); y-axis: relative signal intensity (baseline = 1.0)). IRE: Initial Rate of Enhancement; ME: Maximal Enhancement; IRW: initial rate of washout. b Assignment and color–coding of the voxels within the ROIs based on the shape of the TICs: No enhancement (no color); Persistent (blue); Plateau (green) and Washout (red) represent the most perfused voxels. c Region of interests (ROIs) around the peri-articular knee muscles avoiding major vascular branches. Blue: extensor muscle; Yellow: flexor muscles. d Parametric map of Initial Rate of Enhancement. Brighter colors indicate higher values
Fig. 2
Fig. 2
Flow chart
Fig. 3
Fig. 3
Scatterplots of significant correlations

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