TY - JOUR T1 - The effects of statins on osteoarthritis structural progression: another glimpse of the Holy Grail? JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 633 LP - 634 DO - 10.1136/annrheumdis-2011-201135 VL - 71 IS - 5 AU - Philip G Conaghan Y1 - 2012/05/01 UR - http://ard.bmj.com/content/71/5/633.abstract N2 - While the last 2 decades have seen major advances and novel treatments for inflammatory arthritides, treatments for osteoarthritis (OA) have not advanced. Meanwhile, OA represents a huge problem for both individuals and health economies, with the OA burden rising quickly in ageing Western societies. Recent evidence-based guidelines provide a range of options for pain relief,1 2 often associated with small to moderate effect sizes.3 True structure modification, with its implication for an associated reduction (or at least reduced progression) of symptoms, is often referred to as the Holy Grail of OA research.4 5In the context of chasing this Grail, the interesting report from Clockaerts and colleagues6 adds to a growing strand of research concerning the potential role of statins as structure modifiers in OA. A number of questions arise as a result of this work: Is there a plausible mechanism of action for statins in this context? Is there a real signal of reduced OA structural progression from this and other clinical studies of statins? Statins are best known as competitive inhibitors of hydroxymethyl-glutaryl-coenzyme A reductase that reduce cholesterol biosynthesis. However, for some years it has been recognised that these agents also have significant anti-inflammatory and immune-modulating effects.7,–,9 So, it is possible that these agents may benefit the OA joint through a number of non-mutually exclusive mechanisms on different targets. Inflammation appears universal in symptomatic OA joints, with inflammatory mediators produced by cartilage, bone and synovial cells;10 11 this inflammation is thought to be important in subsequent cartilage degradation. A multitude of anti-inflammatory effects of statins have been reported at the cellular level including inhibition of leucocyte–endothelial adhesion, reduced levels of inducible nitric oxide synthase, inhibition of production and reduced chemoattraction of monocyte chemotactic protein-1, and reduced … ER -