Impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in people at risk of, or with established, knee osteoarthritis

a systematic review and meta-analysis of randomized controlled trials

Alessio Bricca (Corresponding Author), André Struglics, Staffan Larsson, Martijn Steultjens, Carsten B. Juhl, Ewa M. Roos

Research output: Contribution to journalArticle

Abstract

Objective. To investigate the impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in people at risk of, or with established, knee osteoarthritis by conducting a systematic review of randomized controlled trials (RCTs).

Methods. Literature search up to September 2017 in five major databases with no restriction on publication year or language. Data were extracted from the first available follow-up time point and we performed a narrative synthesis for the effect of exercise therapy on molecular biomarkers related to cartilage and inflammation. A subset of studies reporting sufficient data was combined in a meta-analysis, using an adjusted random effects model.

Results. Twelve RCTs, involving 57 study comparisons at 4 to 24 weeks following an exercise therapy intervention were included. Exercise therapy decreased molecular biomarkers in 17 (30%) study comparisons, had no effect in 36 (63%), and increased molecular biomarkers in four (7%) study comparisons. Meta-analyses of nine biomarkers showed that exercise therapy was associated with non-significant reductions of C-reactive protein, C-terminal crosslinking telopeptide of type II collagen, tumor necrosis factor alpha (TNF-α), soluble TNF-α receptor-1 and -2, C2C neoepitope of type II collagen and cartilage oligomeric matrix protein compared to non-exercising control groups and had no effect on interleukin-6 and soluble interleukin 6 receptor.

Conclusions. Exercise therapy is not harmful, as it does not increase the concentration of molecular biomarkers related to cartilage turnover and inflammation, implicated in osteoarthritis progression. The overall quality of evidence was downgraded to low because of the limited number of RCTs available.
Original languageEnglish
JournalArthritis Care & Research
Early online date15 Oct 2018
DOIs
Publication statusE-pub ahead of print - 15 Oct 2018

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Exercise Therapy
Knee Osteoarthritis
Cartilage
Meta-Analysis
Randomized Controlled Trials
Biomarkers
Inflammation
Collagen Type II
Tumor Necrosis Factor-alpha
Cartilage Oligomeric Matrix Protein
Interleukin-6 Receptors
Tumor Necrosis Factor Receptors
Protein C
Osteoarthritis
C-Reactive Protein
Publications
Interleukin-6
Research Design
Language
Databases

Keywords

  • exercise
  • cartilage
  • humans
  • knee
  • molecular biomarkers

Cite this

Impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in people at risk of, or with established, knee osteoarthritis : a systematic review and meta-analysis of randomized controlled trials. / Bricca, Alessio (Corresponding Author); Struglics, André; Larsson, Staffan; Steultjens, Martijn; Juhl, Carsten B.; Roos, Ewa M.

In: Arthritis Care & Research, 15.10.2018.

Research output: Contribution to journalArticle

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abstract = "Objective. To investigate the impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in people at risk of, or with established, knee osteoarthritis by conducting a systematic review of randomized controlled trials (RCTs).Methods. Literature search up to September 2017 in five major databases with no restriction on publication year or language. Data were extracted from the first available follow-up time point and we performed a narrative synthesis for the effect of exercise therapy on molecular biomarkers related to cartilage and inflammation. A subset of studies reporting sufficient data was combined in a meta-analysis, using an adjusted random effects model.Results. Twelve RCTs, involving 57 study comparisons at 4 to 24 weeks following an exercise therapy intervention were included. Exercise therapy decreased molecular biomarkers in 17 (30{\%}) study comparisons, had no effect in 36 (63{\%}), and increased molecular biomarkers in four (7{\%}) study comparisons. Meta-analyses of nine biomarkers showed that exercise therapy was associated with non-significant reductions of C-reactive protein, C-terminal crosslinking telopeptide of type II collagen, tumor necrosis factor alpha (TNF-α), soluble TNF-α receptor-1 and -2, C2C neoepitope of type II collagen and cartilage oligomeric matrix protein compared to non-exercising control groups and had no effect on interleukin-6 and soluble interleukin 6 receptor.Conclusions. Exercise therapy is not harmful, as it does not increase the concentration of molecular biomarkers related to cartilage turnover and inflammation, implicated in osteoarthritis progression. The overall quality of evidence was downgraded to low because of the limited number of RCTs available.",
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author = "Alessio Bricca and Andr{\'e} Struglics and Staffan Larsson and Martijn Steultjens and Juhl, {Carsten B.} and Roos, {Ewa M.}",
note = "This project is supported by a European Union Seventh Framework Programme (FP7-PEOPLE-2013-ITN; KNEEMO) under grant agreement Number 607510. The funding source had no involvement in any aspect of this systematic review and meta-analysis.",
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AU - Bricca, Alessio

AU - Struglics, André

AU - Larsson, Staffan

AU - Steultjens, Martijn

AU - Juhl, Carsten B.

AU - Roos, Ewa M.

N1 - This project is supported by a European Union Seventh Framework Programme (FP7-PEOPLE-2013-ITN; KNEEMO) under grant agreement Number 607510. The funding source had no involvement in any aspect of this systematic review and meta-analysis.

PY - 2018/10/15

Y1 - 2018/10/15

N2 - Objective. To investigate the impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in people at risk of, or with established, knee osteoarthritis by conducting a systematic review of randomized controlled trials (RCTs).Methods. Literature search up to September 2017 in five major databases with no restriction on publication year or language. Data were extracted from the first available follow-up time point and we performed a narrative synthesis for the effect of exercise therapy on molecular biomarkers related to cartilage and inflammation. A subset of studies reporting sufficient data was combined in a meta-analysis, using an adjusted random effects model.Results. Twelve RCTs, involving 57 study comparisons at 4 to 24 weeks following an exercise therapy intervention were included. Exercise therapy decreased molecular biomarkers in 17 (30%) study comparisons, had no effect in 36 (63%), and increased molecular biomarkers in four (7%) study comparisons. Meta-analyses of nine biomarkers showed that exercise therapy was associated with non-significant reductions of C-reactive protein, C-terminal crosslinking telopeptide of type II collagen, tumor necrosis factor alpha (TNF-α), soluble TNF-α receptor-1 and -2, C2C neoepitope of type II collagen and cartilage oligomeric matrix protein compared to non-exercising control groups and had no effect on interleukin-6 and soluble interleukin 6 receptor.Conclusions. Exercise therapy is not harmful, as it does not increase the concentration of molecular biomarkers related to cartilage turnover and inflammation, implicated in osteoarthritis progression. The overall quality of evidence was downgraded to low because of the limited number of RCTs available.

AB - Objective. To investigate the impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in people at risk of, or with established, knee osteoarthritis by conducting a systematic review of randomized controlled trials (RCTs).Methods. Literature search up to September 2017 in five major databases with no restriction on publication year or language. Data were extracted from the first available follow-up time point and we performed a narrative synthesis for the effect of exercise therapy on molecular biomarkers related to cartilage and inflammation. A subset of studies reporting sufficient data was combined in a meta-analysis, using an adjusted random effects model.Results. Twelve RCTs, involving 57 study comparisons at 4 to 24 weeks following an exercise therapy intervention were included. Exercise therapy decreased molecular biomarkers in 17 (30%) study comparisons, had no effect in 36 (63%), and increased molecular biomarkers in four (7%) study comparisons. Meta-analyses of nine biomarkers showed that exercise therapy was associated with non-significant reductions of C-reactive protein, C-terminal crosslinking telopeptide of type II collagen, tumor necrosis factor alpha (TNF-α), soluble TNF-α receptor-1 and -2, C2C neoepitope of type II collagen and cartilage oligomeric matrix protein compared to non-exercising control groups and had no effect on interleukin-6 and soluble interleukin 6 receptor.Conclusions. Exercise therapy is not harmful, as it does not increase the concentration of molecular biomarkers related to cartilage turnover and inflammation, implicated in osteoarthritis progression. The overall quality of evidence was downgraded to low because of the limited number of RCTs available.

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KW - cartilage

KW - humans

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