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SP0181 Bone Loss in RA- Why Both Cytokines and ACPA Matter
  1. G. Schett
  1. University of Erlangen Nuremberg, Erlangen, Germany

Abstract

Rheumatoid arthritis leads to rapid degradation of bone, which translates to bone erosion, premature osteoporosis and increased fracture risk in children, adolescents and adults affected by inflammatory diseases. Understanding the mechanisms of how inflammation impairs bone mass and quality are of seminal importance to prevent the negative consequences of diseases such as arthritis and periodontitis on the bone. In light of the fact that glucocorticoids, despite effectively blunting inflammation, have profound negative consequences on the bone, knowledge on the pathways linking inflammation with bone loss are extremely important for choosing the best anti-rheumatic treatment strategy. Cytokines with well- established function in human inflammatory diseases, such as TNFalpha, IL-1beta and IL-6 distort the balance between bone formation and bone resorption in favor of the latter one. Importantly, all these three principle pro-inflammatory cytokine facilitate the differentiation of bone resorbing osteoclasts from monocyte precursors, thereby inducing enhanced bone resorption. In addition to fostering bone resorption, inhibition of bone formation is a key effect of TNFalpha, which induces the expression of proteins such as Dkk-1 and sclerostin, which are amongst the most potent inhibitors of bone formation in our body. Re-balancing of distorted bone homeostasis is thus of seminal importance for the treatment of inflammatory diseases in both children and adults. Aside inflammatory cytokines, also autoimmunity per se may influence bone balance. For instance, antibodies against citrullinated proteins directly induce the generation of bone resorting osteoclasts and induce bone loss. Rheumatoid arthritis is characterized by autoantibodies against citrullinated proteins (ACPA) recognizing proteins, which have been posttranslationally modified by peptidylarginine deiminases (PAD) that convert arginine to citrulline. ACPA is one of the strongest risk factors for bone destruction in rheumatoid arthritis and is also associated with periodontitis. It is particularly interesting that Porphyromonas gingivalis, a bacterial species of seminal importance for periodontitis contains PAD enzymes and leads to citrullination of proteins. Thus neutralization of inflammatory cytokines may represent only one strategy to inhibit inflammatory bone loss, whereas targeting autoimmunity may be an even better intervention strategy to disrupt the deleterious interaction between inflammation and bone.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.6257

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