The effects of oral glucosamine on joint health: is a change in research approach needed?

Objective: Oral glucosamine (GIcN) has been widely studied for its potential therapeutic benefits in alleviating the pain and disability of osteoarthritis (OA). Its popularity has grown despite ongoing controversy regarding its effectiveness vs placebo in clinical trials, and lack of information regarding possible mechanisms of action. Here, we review the state of knowledge concerning the biology of GIcN as it relates to OA, and discuss a framework for future research directions. Methods: An editorial "narrative" review of peer-reviewed publications is organized into four topics (1) Chemistry and pharmacokinetics of GIcN salts (2) Biological effects of GlcN salts in vitro (3) Therapeutic effects of GIcN salts in animal models of OA and (4) GlcN salts in the treatment of clinical OA. Results: Data reporting potent pleiotropic activities of GIcN in in vitro cell and explant cultures are discussed in the context of the established pharmacokinetic data in humans and animals. The available clinical trial data are discussed to place the patient in the context of controlled research on disease management. Conclusions: Future research to determine therapeutic mechanisms of GIcN salt preparations will require use of standardized and clinically relevant in vitro assay systems and in vivo animal models for testing, as well as development of new outcome measures for inflammation and pain pathways in human OA. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.