Mechanisms of action of therapeutic exercise for knee and hip OA remain a black box phenomenon: an individual patient data mediation study with the OA Trial Bank
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Tom Cochrane,
Inga Krauss,
Ari Heinonen,
Michael Doherty,
Krysia S Dziedzic,
Christine Walker,
May Arna Risberg,
Danielle van der Windt,
Marius Henriksen,
Leigh Hale,
Marienke van Middelkoop,
Rana S Hinman,
Michael A Hunt,
Nadine E Foster,
Melanie A Holden,
Håvard Østerås,
Robert Taylor,
Sita Bierma-Zeinstra,
Kim Bennell,
Benjamin Steinhilber,
Jos Runhaar,
Miriam Hattle,
Carol Ingram,
Jenny Brown,
Kanda Chaipinyo,
Sheila Hickson,
Marijke Hopman-Rock,
Jesper Knoop,
Stephen P Messier,
Helen French,
Cindy Veenhof,
Michael Hurley,
Yusuke Suzuki,
Jason Wallis,
Jonathan Quicke,
Emma Louise Healey,
J Haxby Abbott,
Kelli Allen,
David Bossen,
Mariëtte de Rooij,
Kelley Fitzgerald,
Justin Keogh,
Pazit Levinger,
Christopher McCarthy,
Shahnawaz Anwer,
AnaCristina Rodrigues Lacerda,
Ganesh Shankar,
Laura Talbot,
Carolien Teirlinck,
Pao-Feng Tsai,
Merve Yilmaz Menek
Affiliations
Tom Cochrane
Inga Krauss
Ari Heinonen
Michael Doherty
Academic Rheumatology, University of Nottingham, Nottingham, UK
Krysia S Dziedzic
Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK
Christine Walker
May Arna Risberg
Danielle van der Windt
Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK
Marius Henriksen
The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
Leigh Hale
Marienke van Middelkoop
General Practice, Erasmus MC, Rotterdam, The Netherlands
Rana S Hinman
Michael A Hunt
Nadine E Foster
Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK
Melanie A Holden
Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK
Håvard Østerås
Robert Taylor
Sita Bierma-Zeinstra
General Practice, Erasmus MC, Rotterdam, The Netherlands
Kim Bennell
Benjamin Steinhilber
Jos Runhaar
General Practice, Erasmus MC, Rotterdam, The Netherlands
Miriam Hattle
Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK
Carol Ingram
Jenny Brown
Kanda Chaipinyo
Sheila Hickson
Marijke Hopman-Rock
Jesper Knoop
Stephen P Messier
Helen French
Cindy Veenhof
Michael Hurley
Yusuke Suzuki
Jason Wallis
Jonathan Quicke
Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK
Emma Louise Healey
Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK
Objectives To evaluate mediating factors for the effect of therapeutic exercise on pain and physical function in people with knee/hip osteoarthritis (OA).Methods For Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA), individual participant data (IPD) were sought from all published randomised controlled trials (RCTs) comparing therapeutic exercise to non-exercise controls in people with knee/hip OA. Using the Counterfactual framework, the effect of the exercise intervention and the percentage mediated through each potential mediator (muscle strength, proprioception and range of motion (ROM)) for knee OA and muscle strength for hip OA were determined.Results Data from 12 of 31 RCTs of STEER OA (1407 participants) were available. Within the IPD data sets, there were generally statistically significant effects from therapeutic exercise for pain and physical function in comparison to non-exercise controls. Of all potential mediators, only the change in knee extension strength was statistically and significantly associated with the change in pain in knee OA (β −0.03 (95% CI −0.05 to −0.01), 2.3% mediated) and with physical function in knee OA (β −0.02 (95% CI −0.04 to −0.00), 2.0% mediated) and hip OA (β −0.03 (95% CI −0.07 to −0.00), no mediation).Conclusions This first IPD mediation analysis of this scale revealed that in people with knee OA, knee extension strength only mediated ±2% of the effect of therapeutic exercise on pain and physical function. ROM and proprioception did not mediate changes in outcomes, nor did knee extension strength in people with hip OA. As 98% of the effectiveness of therapeutic exercise compared with non-exercise controls remains unexplained, more needs to be done to understand the underlying mechanisms of actions.