Do Ibuprofen or Glucosamine in Addition to Resistance Exercise Training Improve Muscle Strength in Patients With Knee Osteoarthritis?

Objective: To compare the effects on muscle cross-sectional area (CSA) strength, and function, of treatment with ibuprofen, glucosamine, or placebo in addition to a strength training program, in older adults with knee osteoarthritis (OA). Design: Randomized, controlled, double-blinded 12-week trial. Setting: Community study in Copenhagen, Denmark, in 2005 and 2006. Participants: Patients were recruited through newspaper advertisements. Of the 181 persons screened, 36 (20 women and 16 men) met the inclusion criteria: age 50 to 70 years and bilateral tibiofemoral OA of the knees, based on the American College of Rheumatology clinical and radiographic classification criteria, and with a Kellgren and Lawrence score between 1 and 4. Exclusion criteria were other chronic diseases, contraindication to the study medications, regular exercise training, severe obesity, excess alcohol consumption, and knee injury or previous or planned knee surgery. Intervention: Participants were instructed not to take ibuprofen and/or glucosamine for 1 month before the study. They were randomized to receive 500 mg of glucosamine sulfate 3 times per day, 600 mg of ibuprofen 2 times per day, or placebo. All patients were instructed to take 5 tablets per day (active and/or placebo) to maintain blinding, beginning 4 weeks before the exercise intervention so that training could be preceded by 4 weeks of glucosamine and 1 week of active ibuprofen. Acupuncture or 50 mg of tramadol was permitted for severe pain. The 12-week strength training program (45-minute supervised sessions, 3 per week) comprised progressive unilateral training for both legs focusing on the quadriceps muscle, using leg press and knee extension machines. Main Outcome Measures: Quadriceps muscle CSA was measured using magnetic resonance imaging. Isometric, concentric, and eccentric quadriceps strength was assessed using an isokinetic dynamometer. Maximal unilateral leg extension power was measured using a Nottingham Power Rig (Medical Engineering Unit, University of Nottingham, United Kingdom). Muscle strength was also measured as the greatest load that could be lifted 5 times without resting, on the knee extension and the leg press machines. Function was assessed as walking speed, stair-climbing time, and speed of chair stands. Pain was rated during strength measurements using a visual analog scale (VAS). All measures were done 2 to 4 days before and again after the 12 weeks of training. Main Results: After 12 weeks, CSA of the quadriceps muscle increased for all groups (P ≤ 0.05) but did not differ among them. In comparison with the placebo group, the ibuprofen group increased more in maximal isometric strength (difference, 0.22 Nm/kg; 95% confidence interval [CI], 0.01-0.42; P = 0.04), in maximal eccentric muscle strength (difference, 0.38 Nm/kg; 95% CI, 0.05-0.70; P = 0.02), and in maximal eccentric work (difference, 0.27 J/kg; 95% CI, 0.01-0.53; P = 0.04). In comparison with the placebo group, the glucosamine group increased more in maximal concentric muscle work (difference, 0.24 J/kg; 95% CI, 0.06-0.42; P = 0.01). On other measures of strength and power, the groups did not differ. Strength on the knee extension and leg press machines increased for both the ibuprofen and glucosamine groups (P < 0.05) but did not differ from placebo. No differences between groups were found on the measures of function, but all groups improved from baseline. Compared with placebo, both ibuprofen (difference, 0.82 points; 95% CI, 0.23-1.42; P < 0.01) and glucosamine (difference, 0.79 points; 95% CI, 0.24-1.33; P < 0.01) reduced reported pain (VAS) during the strength assessment. Satellite cell number increased in the glucosamine and placebo groups but not in the ibuprofen group. Conclusions: Quadriceps muscle mass increased with 12 weeks of strength training and was not affected by taking ibuprofen or glucosamine. The supplements did increase some measures of muscle strength and reduced pain while training.

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