Background/Purpose: Inflammation in osteoarthritis (OA) has been characterized by infiltration of immune cells and secretion of cytokines into synovial tissues. Noradrenaline levels, sympathetic nerve fiber distribution and β2-AR expression in the bone of rats have been associated with subchondral bone loss and increased osteoclast activity. All these data suggest the participation of the adrenergic and immune systems in the development and evolution of OA. However, the relationship among the systemic adrenergic and immune systems activation with OA progression and treatment response is less well known.

Methods: Serum samples from patients participants in a 6-month controlled, double blind and randomized clinical trial comparing the efficacy of pharmaceutical grade Chondroitin sulfate/Glucosamine hydrochloride (CS/GH) and Celecoxib (CE) were analyzed to determine cytokines (IL-2, IL-4, IL-6, IL-10, IL-8, IL-1beta using BD™ Cytometric Bead Array (CBA) immunoassay), catecholamines (noradrenaline, adrenaline and dopamine using ELISA LDN®) and the presence of endotoxin or lipopolysaccharide (LPS; LAL test Lonza®).

Results: Samples from 100 knee OA patients (age: 62±8 yr.; BMI: 31±6 kg/m²; 86 females; VAS: 73±15; WOMAC: 369±43) treated with CS/GH (50) or CE (50) were analyzed. There were no baseline differences between treatment groups. After 6 months of treatment, both groups of patients showed a similar reduction in VAS and WOMAC score (Table 1). Serum IL-2, IL-4, IL-6, IL-8, IL-10 and dopamine levels did not change significantly over tretament. Adrenaline levels were significantly reduced by both treatments. Moreover, serum noradrenaline was reduced only in the group treated with CS/GH although the difference was not significant because of the great data variability. LPS levels were doubled in both treatment groups but attained values remained very low and were accompanied by a small and non-significant increase in IL-1 beta (p=0.07). These effects were similar in patients who attained a clinically meaningful VAS score decrease compared with those who didn’t.

Conclusion: Six month treatment with CS/GH reduces significantly and in a similar fashion to NSAID CE the pain intensity and systemic adrenergic activation in patients with OA. Reduction in adrenergic activation was independent of pain response. Further studies are needed to ascertain the relationship between systemic adrenergic changes and subchondral bone loss and osteoclast activity.

Table 1.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/chondroitin-sulfateglucosamine-hydrochloride-induce-a-reduction-in-adrenergic-serum-markers-in-osteoarthritis-patients-similar-to-that-produced-by-celecoxib/