Mechanisms and therapeutic targets for bone damage in rheumatoid arthritis, in particular the RANK-RANKL system

Curr Opin Pharmacol. 2018 Jun:40:110-119. doi: 10.1016/j.coph.2018.03.006. Epub 2018 Apr 24.

Abstract

Rheumatoid arthritis (RA), a chronic inflammatory disorder, causes swelling, bone erosion, and joint deformity. Bone erosion in RA-affected joints arises from activation of osteoclasts by inflammatory processes. RA patients may also have primary, disease-related, or glucocorticoid-induced osteoporosis, caused by a disrupted balance between osteoclasts and osteoblasts. Disease-modifying antirheumatic drugs (DMARDs) interfere with the processes causing inflammation in the joint but do not sufficiently treat bone erosion and osteoporosis. Denosumab, an inhibitor of receptor activator of nuclear factor κ-B ligand (RANKL), protects bones in osteoporosis patients. Clinical studies have demonstrated that denosumab can also prevent bone erosion in RA patients. Because joint destruction progresses in some patients treated with DMARDs alone, denosumab will likely become standard treatment for some RA patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / physiopathology
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Remodeling / drug effects*
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Bone and Bones / physiopathology
  • Denosumab / adverse effects
  • Denosumab / therapeutic use*
  • Humans
  • Molecular Targeted Therapy / methods*
  • RANK Ligand / antagonists & inhibitors*
  • RANK Ligand / metabolism
  • Receptor Activator of Nuclear Factor-kappa B / metabolism*
  • Signal Transduction / drug effects

Substances

  • Bone Density Conservation Agents
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFSF11 protein, human
  • Denosumab