ORIGINAL ARTICLE Nonsteroidal Anti-Inflammatory Drug or Glucosamine Reduced Pain and Improved Muscle Strength With Resistance Training in a Randomized Controlled Trial of Knee Osteoarthritis Patients Susanne G. Petersen, MD, Nina Beyer, PhD, Mette Hansen, PhD, Lars Holm, PhD, Per Aagaard, Dr Med, MD, Abigail L. Mackey, PhD, Michael Kjaer, PhD, MSc ABSTRACT. Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients. Arch Phys Med Rehabil 2011;92:1185-93. Objectives: To investigate the effect of 12 weeks of strength training in combination with a nonsteroidal anti-inflammatory drug (NSAID), glucosamine, or placebo on muscle cross- sectional area (CSA), strength (primary outcome parameters), and function, power, pain, and satellite cell number (secondary outcome parameters) in patients with knee osteoarthritis (OA). Design: Double-blinded, randomized controlled trial. Setting: Hospital. Participants: Patients (N=36; 20 women, 16 men; age range, 50 –70y) with bilateral tibiofemoral knee OA. A total of 181 patients were approached, and 145 were excluded. Interventions: Patients were randomly assigned to treat- ment with the NSAID ibuprofen (n=12), glucosamine (n=12), or placebo (n=12) during 12 weeks of quadriceps muscle strength training. Main Outcome Measures: Muscle CSA and strength. Results: No differences between groups were observed in gains in muscle CSA. Training combined with ibuprofen in- creased maximal isometric strength by an additional .22Nm/kg (95% confidence interval [CI], .01–.42; P=.04), maximal ec- centric muscle strength by .38Nm/kg (95% CI, .05–.70; P=.02), and eccentric muscle work by .27J/kg (95% CI, .01– .53; P=.04) in comparison with placebo. Training combined with glucosamine increased maximal concentric muscle work by an additional .24J/kg versus placebo (95% CI, .06 –.42; P=.01). Conclusions: In patients with knee OA, NSAID or gluco- samine administration during a 12-week strength-training pro- gram did not improve muscle mass gain, but improved maxi- mal muscle strength gain in comparison with treatment with placebo. However, we do not find that the benefits are large enough to justify taking NSAIDs or glucosamine. Key Words: Dietary supplements; Exercise; Ibuprofen; Re- habilitation; Satellite cells; skeletal muscle. © 2011 by the American Congress of Rehabilitation Medicine O STEOARTHRITIS (OA) IS THE most common joint disease, affecting not only the joints but also the surround- ing muscles, which become weak. 1 Reduced quadriceps strength appears to be a risk factor as well as a consequence of OA of the knee. 2-5 Exercise reduces pain and improves func- tion in patients with OA of the knee, 6-8 and these beneficial effects are observed in exercise interventions including strength or endurance training. 9-14 However, knowledge of the mechanisms responsible for the beneficial effects of physical training is limited. Specifically, information on the effect of strength training on muscle strength, hypertrophy, and mor- phology in patients with knee OA is scarce. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used by patients with OA to reduce pain and thereby maintain the ability to perform daily activities. However, in young, healthy individuals, there is accumulating evidence for a neg- ative effect of NSAIDs on skeletal muscle adaptation to phys- ical training. 15-21 NSAIDs are reported to attenuate the increase in muscle protein synthesis in young men after an acute bout of resistance exercise, probably by inhibiting cyclooxygenase ac- tivity. 15-17 Additionally, muscle satellite cell activity, which facilitates muscle hypertrophy, is negatively regulated by NSAIDs after an acute bout of resistance exercise 18 or endur- ance exercise in humans. 19 In rats, NSAIDs have been reported to severely blunt skeletal muscle hypertrophy after a period of From the Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Centre for Healthy Ageing, Faculty of Health Sciences, University of Copenhagen, Copenhagen (Petersen, Beyer, Hansen, Holm, Mackey, Kjaer); and Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense (Aagaard), Denmark. Supported by the Nordea Foundation (Centre for Healthy Aging Grant), MYOAGE (grant no. 223576) funded by the European Commission under the Seventh Frame- work Programme, Danish Rheumatism Association, Danish Ministry of Health (grant no. 2006-1022-61), IMK Almene Fond (grant no. 30206-158), and Lundbeck Foun- dation (grant no. A1385). No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organi- zation with which the authors are associated. Clinical Trial Registration Number: NCT00833157. Reprint requests to Susanne G. Petersen, MD, Institute of Sports Medicine, Bispe- bjerg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Denmark, e-mail: susannegp@gmail.com.dk. 0003-9993/11/9208-00831$36.00/0 doi:10.1016/j.apmr.2011.03.009 List of Abbreviations AE adverse event CI confidence interval CRP C-reactive protein CSA cross-sectional area KinCom Kinetics Communicator KOOS Knee Injury and Osteoarthritis Outcome Score MD medical doctor NSAID nonsteroidal anti-inflammatory drug OA osteoarthritis RM repetition maximum SEM standard error of the mean VAS visual analog scale 1185 Arch Phys Med Rehabil Vol 92, August 2011