The use of glucocorticoids in rheumatoid arthritis--no 'rational' approach yet

Abstract

The relationship between glucocorticoids and bone mineral density in rheumatoid arthritis is complex. Further study into the optimal dosing, timing and duration of glucocorticoid use in rheumatoid arthritis is necessary.

Figure 1

Osteoclast formation in the joint. Monocytic cells in the synovium serve as osteoclast precursors. Upon exposure to macrophage colony-stimulating factor (MCSF) and Receptor activator of nuclear factor-kappa B ligand (RANKL) synthesized by T cells and synovial fibroblasts, osteoclasts fuse to polykaryons termed preosteoclasts, which then undergo further differentiation into mature osteoclasts, acquiring specific features such as the ruffled membrane. Inflammatory cytokines such as TNF and IL-1, IL-6, and IL-17 increase the expression of RANKL and thus support osteoclastogenesis in the joint. In contrast, regulatory T cells (Tregs) block osteoclast formation via Cytotoxic T-lymphocyte antigen 4 (CTLA4). Figure obtained with permission from [3].

Figure 2

The direct and indirect effects of glucocorticoids on bone leading to glucocorticoid-induced osteoporosis and fractures. Figure obtained with permission from [4]. CSF, colony stimulating factor; GH, growth hormone; IGF, insulin-like growth factor; RANKL, Receptor activator of nuclear factor-kappa B ligand.