Does Knee Malalignment Mediate the Effects of Quadriceps Strengthening on Knee Adduction Moment, Pain, and Function in Medial Knee Osteoarthritis? A Randomized Controlled Trial BOON-WHATT LIM, 1 RANA S. HINMAN, 1 TIM V. WRIGLEY, 1 LEENA SHARMA, 2 AND KIM L. BENNELL 1 Objective. To examine whether the effects of 12 weeks of quadriceps strengthening on the knee adduction moment, pain, and function in people with medial knee osteoarthritis (OA) differ in those with and without varus malalignment. Methods. A single-blind, randomized controlled trial of 107 community volunteers with medial knee OA was conducted. Participants were stratified according to knee malalignment (more varus or more neutral) and then randomized into either a 12-week supervised home-based quadriceps strengthening group or a control group with no intervention. The primary outcome was the knee adduction moment, measured using 3-dimensional gait analysis. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index scores (measuring pain and physical function), step test score, stair climb test score, and maximum quadriceps isometric strength. Analyses of covariance were carried out based on intent-to-treat principles. Results. Quadriceps strengthening did not significantly alter the knee adduction moment in either the more malaligned or the more neutral group (unadjusted knee adduction moment 0.12 and 0.05% Nm/BWHT, respectively). Function did not improve significantly following quadriceps strengthening in either alignment group, but there was a significant improvement in knee pain in the more neutrally aligned group (P < 0.001). Conclusion. Quadriceps strengthening did not have any significant effect on the knee adduction moment in participants with either more varus or more neutral alignment. The benefits of quadriceps strengthening on pain were more evident in those with more neutral alignment. Knee alignment thus represents a local mechanical factor that can mediate symptomatic outcome from exercise interventions in knee OA. INTRODUCTION Mechanical factors have been implicated in the etiology and progression of knee osteoarthritis (OA) (1,2). In par- ticular, knee alignment is thought to play an important role (3,4). Knee alignment determines load distribution across the knee. During normal gait, 70% of knee joint loading passes through the medial compartment (5) due to the ground reaction force passing medial to the knee joint. Malalignment is a local joint factor that can affect how well the knee copes with imposed forces. Varus malalign- ment, commonly associated with medial tibiofemoral OA, serves to increase the moment arm of the ground reaction force and further increase loading in the medial compart- ment (6,7). As a result, varus malalignment is a major contributing factor to OA progression in this compartment (4,8,9). Quadriceps strengthening exercises are commonly pre- scribed for patients with knee OA because they can reduce pain and improve function (10 –12). However, little is known about their effects on knee loading and disease progression, and it is unclear whether these effects are influenced by the presence of knee malalignment. A recent longitudinal study found that greater quadriceps strength at baseline increased the risk of disease progression in patients with malaligned knees but not in those with neu- ClinicalTrials.gov identifier: NCT00414557. Supported in part by United Pacific Industries through a grant from the Physiotherapy Research Foundation, Austra- lia. 1 Boon-Whatt Lim, BSc(Hons)Physio, MSc, Rana S. Hin- man, BPhysio(Hons), PhD, Tim V. Wrigley, MSc, Kim L. Bennell, BAppSc(Physio), PhD: Center for Health, Exercise, and Sports Medicine, School of Physiotherapy, The Univer- sity of Melbourne, Victoria, Australia; 2 Leena Sharma, MD: Feinberg School of Medicine, Northwestern University, Chi- cago, Illinois. Address correspondence to Kim L. Bennell, BAppSc (Physio), PhD, Center for Health, Exercise, and Sports Med- icine, School of Physiotherapy, The University of Mel- bourne, 202 Berkeley Street, Carlton 3010, Melbourne, Vic- toria, Australia. E-mail: k.bennell@unimelb.edu.au. Submitted for publication September 17, 2007; accepted in revised form February 11, 2008. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 59, No. 7, July 15, 2008, pp 943–951 DOI 10.1002/art.23823 © 2008, American College of Rheumatology ORIGINAL ARTICLE 943