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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

Runhaar, Jos; A Holden, Melanie; Hattle, Miriam; Quicke, Jonathan; Healey, Emma Louise; van der Windt, Danielle; Dziedzic, Krysia S; van Middelkoop, Marienke; Bierma-Zeinstra, Sita; Foster, Nadine E; Brown, Jenny; Ingram, Carol; Hickson, Sheila; Taylor, Robert; Walker, Christine; Haxby Abbott, J; Allen, Kelli; Hurley, Michael; Bennell, Kim; Bossen, David; Chaipinyo, Kanda; Cochrane, Tom; Rooij, Mariëtte de; Risberg, May Arna; Fitzgerald, Kelley; French, Helen; Hale, Leigh; Henriksen, Marius; Hinman, Rana S; Hopman-Rock, Marijke; Keogh, Justin; Veenhof, Cindy; Knoop, Jesper; Krauß, Inga; Levinger, Pazit; McCarthy, Christopher; Messier, Stephen P; Heinonen, Ari; Osteras, Havard; Anwer, Shahnawaz; Lacerda, AnaCristina Rodrigues; Shankar, Ganesh; Steinhilber, Benjamin; Suzuki, Yusuke; Hunt, Michael A; Talbot, Laura; Teirlinck, Carolien; Doherty, Michael; Tsai, Pao-Feng; Wallis, Jason; Menek, Merve Yilmaz


Jos Runhaar

Miriam Hattle

Jonathan Quicke

Marienke van Middelkoop

Sita Bierma-Zeinstra

Nadine E Foster

Jenny Brown

Carol Ingram

Sheila Hickson

Robert Taylor

Christine Walker

J Haxby Abbott

Kelli Allen

Michael Hurley

Kim Bennell

David Bossen

Kanda Chaipinyo

Tom Cochrane

Mariëtte de Rooij

May Arna Risberg

Kelley Fitzgerald

Helen French

Leigh Hale

Marius Henriksen

Rana S Hinman

Marijke Hopman-Rock

Justin Keogh

Cindy Veenhof

Jesper Knoop

Inga Krauß

Pazit Levinger

Christopher McCarthy

Stephen P Messier

Ari Heinonen

Havard Osteras

Shahnawaz Anwer

AnaCristina Rodrigues Lacerda

Ganesh Shankar

Benjamin Steinhilber

Yusuke Suzuki

Michael A Hunt

Laura Talbot

Carolien Teirlinck

Michael Doherty

Pao-Feng Tsai

Jason Wallis

Merve Yilmaz Menek


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.

Journal Article Type Article
Acceptance Date Jul 24, 2023
Online Publication Date Aug 28, 2023
Publication Date 2023-08
Deposit Date Sep 7, 2023
Publicly Available Date Sep 7, 2023
Journal RMD Open
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 9
Issue 3
Article Number e003220
Keywords Osteoarthritis, Rehabilitation, Physical Therapy Modalities


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 (433 Kb)


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