Statins and the joint: multiple targets for a global protection?

OBJECTIVES: Evidence exists that the pleiotropic properties of the hydroxy-methyl-glutaryl Coenzyme A reductase inhibitors (statins) are not restricted to the cardiovascular system, as they can also favorably affect the joints, with intriguing implications for the treatment of many rheumatic diseases. In the view of the increasing interest on this topic, we here review the current state of the art. METHODS: The PubMed database was searched for articles published between 1966 and 2010 for key words referring to statins and joint diseases. All relevant English-written articles were reviewed. RESULTS: Many pivotal studies clearly demonstrated that HMG-CoA reductase inhibitors exert a wide spectrum of beneficial effects on the 3 main compartments of the joint, ie, the synovium, the cartilage, and the subchondral bone. Such (1) anti-inflammatory, (2) immunomodulating, and (3) anabolic effects strongly support a potential role of these drugs in the treatment and/or the prevention of the most important chronic joint diseases. However, although the majority of the in vivo studies with statins on animal models of inflammatory and degenerative joint diseases showed a marked protective activity substantially confirming the in vitro experiments, data arising from clinical trials are less probative and more conflicting. CONCLUSIONS: Statins display multiple joint-protective effects. Since oral administration of statins could result in a relatively low drug bioavailability to the joints, alternative routes of administration of the drug (transdermal, intra-articular) and/or specific delivery systems should be developed to establish the entire therapeutic potential of statins in this clinical setting.