Bone Involvement in Rheumatoid Arthritis and Spondyloartritis: An Updated Review

Abstract

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

Keywords: bone tissue; erosions; new bone formation; osteoimmunology; rheumatoid arthritis; spondyloarthritis.

Figure 1

Cellular and molecular interplay involved in the pathogenesis of bone damage in rheumatoid arthritis. ACPAs, anti-citrullinated protein antibodies; RANKL, receptor activator of nuclear factor kappa-Β ligand; OPG, osteoprotegerin; TNFα, tumor necrosis factor-alpha; FLS, fibroblast-like synoviocytes; NETs, neutrophil extracellular traps; MMPs, matrix metalloproteinases; FcγR, fc gamma receptor; IL-1, interleukin-1; IL-6, interleukin-6; IL-17, interleukin 17.

Figure 2

Interaction between the immune system, osteoclasts, and osteoblasts in the pathogenesis of bone involvement in spondyloarthritis. MSC, mesenchymal stromal cells; ILC, innate lymphoid cells; hPBMCs, human peripheral blood mononuclear cells; HLA-B27, human leukocyte antigen-B27; RANKL, receptor activator of nuclear factor kappa-Β ligand; OPG, osteoprotegerin; DKK1, Dickkopf-related protein 1; TNFα, tumor necrosis factor-alpha; TNFR1-2, tumor necrosis factor receptor 1-2; IL-1, interleukin-1; IL-6, interleukin-6; IL-17A, interleukin-17A; IL-22, interleukin-22; IL-23, interleukin-23.