OBJECTIVE: Glucosamine, classified as a slow-acting drug in osteoarthritis 
(SADOA), is an efficacious chondroprotective agent. Methylsulfonylmethane (MSM), 
the isoxidised form of dimethyl-sulfoxide (DSMO), is an effective natural 
analgesic and anti-inflammatory agent. The aim of this study was to compare the 
efficacy and safety of oral glucosamine (Glu), methylsulfonylmethane (MSM), 
their combination and placebo in osteoarthritis of the knee.
PATIENTS AND DESIGN: A total of 118 patients of either sex with mild to moderate 
osteoarthritis were included in the study and randomised to receive either Glu 
500mg, MSM 500mg, Glu and MSM or placebo capsules three times daily for 12 
weeks. Patients were evaluated at 0 (before drug administration), 2, 4, 8 and 12 
weeks post-treatment for efficacy and safety. The efficacy parameters studied 
were the pain index, the swelling index, visual analogue scale pain intensity, 
15m walking time, the Lequesne index, and consumption of rescue medicine.
RESULTS: Glu, MSM and their combination significantly improved signs and 
symptoms of osteoarthritis compared with placebo. There was a statistically 
significant decrease in mean (+/- SD) pain index from 1.74 +/- 0.47 at baseline 
to 0.65 +/- 0.71 at week 12 with Glu (p < 0.001). MSM significantly decreased 
the mean pain index from 1.53 +/- 0.51 to 0.74 +/- 0.65, and combination 
treatment resulted in a more significant decrease in the mean pain index (1.7 
+/- 0.47 to 0.36 +/- 0.33; p < 0.001). After 12 weeks, the mean swelling index 
significantly decreased with Glu and MSM, while the decrease in swelling index 
with combination therapy was greater (1.43 +/- 0.63 to 0.14 +/- 0.35; p < 0.05) 
after 12 weeks. The combination produced a statistically significant decrease in 
the Lequesne index. All treatments were well tolerated.
CONCLUSION: Glu, MSM and their combination produced an analgesic and 
anti-inflammatory effect in osteoarthritis. Combination therapy showed better 
efficacy in reducing pain and swelling and in improving the functional ability 
of joints than the individual agents. All the treatments were well tolerated. 
The onset of analgesic and anti-inflammatory activity was found to be more rapid 
with the combination than with Glu. It can be concluded that the combination of 
MSM with Glu provides better and more rapid improvement in patients with 
osteoarthritis.