Erosive arthritis

Abstract

Inflammation and degradation of bone are two closely linked processes. Chronic inflammatory arthritis not only leads to inflammatory bone loss but it also involves local erosion of articular bone. This osteo-destructive feature of chronic inflammatory arthritis is a major cause of disability in patients with rheumatoid arthritis. Osteoclasts are essential for the resorption of mineralized cartilage and subchondral bone in chronic arthritis. The observed up-regulation of osteoclast differentiation factors (receptor activator of nuclear factor-kappaB ligand [RANKL]) in the synovial membrane of chronically inflamed joints indicates that osteoclasts are abundant in this setting, leading to rapid degradation of mineralized tissue. Blockade of osteoclast formation is thus a key strategy in preventing structural damage in arthritis. Denosumab, a humanized antibody that neutralizes RANKL, is an attractive candidate agent to inhibit inflammatory bone loss.

Figure 1

Hand radiograph of a patient with rheumatoid arthritis. Imaged is the hand of a patient with advanced rheumatoid arthritis with severe destruction of the joint architecture. Asterisks indicate bone erosion.

Figure 2

Microphotograph of human bone erosion. Tartrate acid phosphatase staining through a finger joint of patient with rheumatoid arthritis shows osteoclasts (inset) resorbing the mineralized cartilage.

Figure 3

Scheme of arthritic bone erosion. In synovial inflammatory tissue the interaction of fibroblasts, T cells, and monocytes leads to differentiation of osteoclast precursor cells and mature osteoclasts; this results in destruction of mineralized tissue, including cartilage and cortical bone.

Figure 4

Effect of RANKL blockade on experimental arthritis. Adjuvant-induced arthritis of rats treated with vehicle or osteoprotegerin (OPG). Note the protection of bone and the absence of (stained) osteoclasts. RANKL, receptor activator of nuclear factor-κB ligand.