Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases

Abstract

Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases.

Figure 1

The role of inflammatory cytokine network in inflammatory bone loss. Bone remodeling is tightly regulated by the balanced action between bone-forming osteoblasts and bone-resorbing osteoclasts. In chronic inflammatory condition, inflammatory cytokine networks induce an uncoupling of bone formation and resorption that result in significant inflammatory bone loss. RANK: receptor activator of nuclear factor κB. RANKL: RANK ligand. OPG: osteoprotegerin. Runx2: runt-related transcription factor 2. TRAP: tartrate-resistant acid phosphatase. NFATc1: nuclear factor of activated T cells cytoplasmic 1. v-ATPase: vacuolar-type H⁺-ATPase. MMP: matrix metalloproteinase. Ctsk: cathepsin K.