Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

Abstract

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

Keywords: DMARD; biologics; joint destruction; osteoporosis; rheumatoid arthritis.

Figure 1

Bone formation and resorption. Osteoblasts and osteocytes differentiate from mesenchymal stem cells to produce bone matrix. Osteoclasts derived from hematopoietic stem cells mature to multinucleated osteoclasts in response to stimulation by RANKL expressed in osteoblasts and osteocytes.

Figure 2

Rheumatoid synovium by ultrasonography and bone erosion by MR-imaging. Synovial hypertrophy (white bar) by systematic multiplanar grayscale ultrasonography (A), marked signals of synovial flow by power doppler ultrasonography (B), bone erosion ((C), yellow bar) and synovial hypertrophy ((C), orange bar) by MR-imaging are characteristic images in rheumatoid arthritis.

Figure 3

Osteoporosis and bone erosion in rheumatoid arthritis. Osteoclasts in the rheumatoid synovium deviate from normal bone metabolism by stimulation with tumor necrosis factor (TNF), IL-6, and T-cells, and cause bone destruction by the maturation and activation of osteoclasts in an osteoblast-independent manner, leading to bone erosion.

Figure 4

Dendritic-cell-derived osteoclasts in rheumatoid arthritis. Osteoclasts derived from dendritic cells by stimulation of GM-CSF, M-CSF, and RANKL played pathological roles in chronic inflammatory and destructive synovitis via osteoclastic bone resorption, as well as costimulatory activation of T cells.

Figure 5

Osteoporosis, bone erosion, cartilage resorption, and synovial inflammation in rheumatoid arthritis, with their corresponding targets.