Background/Purpose: Non-steroidal anti-inflammatory drugs, e.g., celecoxib, are commonly used for inflammatory conditions, including osteoarthritis (OA), but are associated with adverse effects. Combined glucosamine hydrochloride plus chondroitin sulfate (GH+CS) is commonly used for joint pain and has no known adverse side effects. Evidence from in vitro, animal and human studies suggests that GH and CS have anti-inflammatory activity, among other mechanisms of action.

Methods: In this study, we evaluated a panel of 20 serum proteins involved in inflammation and other metabolic signaling pathways after treatment with pharmaceutical grade 1500 mg GH + 1200 mg CS daily (n=96) versus 200 mg celecoxib once a day (n=93) in a 6-month randomized, parallel, double-blind trial of knee OA patients. All patients had Kellgren and Lawrence grades 2-3 knee OA and moderate-to-severe pain as defined by Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥ 301; on a 0-500 scale. We used linear mixed models adjusted for age, sex, body mass index, baseline serum protein values, and rescue medicine use to assess the intervention effects of each treatment arm separately and between treatments. Benjamini-Hochberg FDR (q<0.05) was used to control for multiple testing.

Results: When evaluating treatments separately, all serum proteins except WNT16 were lower after treatment with GH+CS, while about half of the proteins increased after celecoxib. IL-6 was statistically significantly reduced (by 9%, P=0.001) after GH+CS, and satisfied the FDR threshold of q<0.05. There were statistically significant increases for CCL20, CSF3, and WNT16 after celecoxib (by 7%, 9% and 9%, respectively, P<0.05), but these proteins were no longer statistically significant after controlling for multiple testing. There were no statistically significant differences in any proteins when comparing serum protein concentrations at end of treatment between GH+CS and celecoxib.

Conclusion: The results of this study demonstrate that GH+CS reduces IL-6, an inflammatory cytokine, but is otherwise comparable to celecoxib with regard to effects on other protein biomarkers.

Trial registration number: NCT01425853.

Table 1. Protein biomarker effect sizes after 6 month treatment with combined glucosamine and chondroitin (GH+CS) and celecoxib

Values represent effect sizes in biomarker values pre-to-post intervention from: ¹paired t-tests (unadjusted models with the exception of hybridization and plate day); ² linear mixed regression models adjusted for sex, age, BMI, baseline biomarker values, use of rescue medication, and hybridization and plate day.

³Values represent differences between GH+CS to celecoxib.

⁴This biomarker failed to hybridize for a large proportion of samples and was excluded from analysis.

*Significant with Benjamini-Hochberg FDR q<0.05