Inflammation and Bone Metabolism in Rheumatoid Arthritis: Molecular Mechanisms of Joint Destruction and Pharmacological Treatments

Int J Mol Sci. 2022 Mar 6;23(5):2871. doi: 10.3390/ijms23052871.


Rheumatoid arthritis (RA) is an inflammatory disease characterized by a variety of symptoms and pathologies often presenting with polyarthritis. The primary symptom in the initial stage is joint swelling due to synovitis. With disease progression, cartilage and bone are affected to cause joint deformities. Advanced osteoarticular destruction and deformation can cause irreversible physical disabilities. Physical disabilities not only deteriorate patients' quality of life but also have substantial medical economic effects on society. Therefore, prevention of the progression of osteoarticular destruction and deformation is an important task. Recent studies have progressively improved our understanding of the molecular mechanism by which synovitis caused by immune disorders results in activation of osteoclasts; activated osteoclasts in turn cause bone destruction and para-articular osteoporosis. In this paper, we review the mechanisms of bone metabolism under physiological and RA conditions, and we describe the effects of therapeutic intervention against RA on bone.

Keywords: CTLA-4; DKK-1; IL-6; JAK; RANKL; TNF-α; fibroblast; osteoclast; osteoporosis; rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid* / metabolism
  • Humans
  • Inflammation / pathology
  • Osteoclasts / metabolism
  • Quality of Life
  • RANK Ligand / metabolism
  • Synovitis*


  • RANK Ligand