Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids

Table 1

Characteristics and results of selected placebo-controlled trials.

Author(s), year	Agent/Doses	Duration	Pts (𝑛)	Outcome measure	Results and conclusion
Bruyere et al. 2008 (follow-up of two RCTs 2001/02-see below) [27]	GlcN·S/1500 mg	Formerly: 3 yrs; Now: mean 5 yrs after trial termination	340∗(275=81% retrieved) GlcN⋅S: 144 Plac: 131∗ at least 12-month treatment	Incidence of total knee replacement	Formerly: knee OA progression reduced, structure- and symptom-modifying effects; Now: 6.3% of GlcN·S pts underwent total knee replacement surgery versus 14.5% of the plac. pts 𝑃=0.026; Risk of total knee replacement could be reduced 5 yrs after drug discontinuation.
Clegg et al. 2006 (GAIT, Glucosamine/Chondroitin Arthritis Intervention Trial) [28]	GlcN·HCl/1500 mg CS/1200 mg Celecoxib 200 mg	6 months	1583	20% reduction of knee pain	GlcN·HCl + CS: 66.4% of pts. had 20% pain reduction versus Plac: 61.1% of pts. 𝑃=0.09—n.s.
			354 (subgroup with moderate-to-severe pain)	20% reduction of knee pain	GlcN⋅HCl + CS: 79,2% versus Plac. 54.3% 𝑃=0.002; Combination of GlcN⋅HCl + CS was effective in reducing moderate-to-severe pain in knee OA.
Herrero-Beaumont et al. 2007 (GUIDE, Glucosamine Unum In Die Efficacy) [29]	GlcN·S/1500 mg Acetaminophen 3000 mg	6 months	318 GlcN·S 106; Acet. 108	OARSI-A responder (relative change WOMAC pain subscale of at least 55%)	GlcN·S: 39.6% versus plac. 21.2% 𝑃=0.004; Acet.: n.s.; GlcN·S was superior to plac. in the treatment of knee OA
Reginster et al. 2001 [30]	GlcN·S/1500 mg	3 yrs	212: GlcN·S 106	Radiographs of the knee: joint spacenarrowing; Lequ. index, WOMAC score	GlcN·S: no significant joint space loss, WOMAC score reduction; Plac.: progressive joint space narrowing, WOMAC score increased: Structure- and symptom-modifying effects
Pavelka et al. 2002 [31]	GlcN·S/1500 mg	3 yrs	202: GlcN·S 101	Radiographs of the knee: joint space narrowing; Lequ. index, WOMAC score	GlcN·S: no significant joint space loss; Plac.: progressive joint space narrowing 𝑃=0.001 GlcN⋅S: Lequ. and WOMAC scores improved by 20% to 25%; Structure- and symptom-modifying effects
Bruyere et al. 2004 [32]	GlcN·S 1500 mg	3 yrs	319 postmenopausal women (of 414 pts of two RCTs, see above)	Radiographs of the knee: joint space narrowing; WOMAC score	GlcN⋅S: no significant joint space loss Plac.: progressive joint space narrowin 𝑃<0.0001; WOMAC score reduction: “Pain” (𝑃<0.02) and “Function” (𝑃<0.004)