Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by the presence of symmetric polyarthritis predominantly of the small joints that leads to severe cartilage and bone destruction. Based on animal and human data, the pathophysiology of osteoporosis, a frequent comorbidity in conjunction with RA, was delineated. Autoimmune inflammatory processes, which lead to a systemic upregulation of inflammatory and osteoclastogenic cytokines, the production of autoantibodies, and Th cell senescence with a presumed disability to control the systemic immune system's and osteoclastogenic status, may play important roles in the pathophysiology of osteoporosis in RA. Consequently, osteoclast activity increases, osteoblast function decreases and bone metabolic and mechanical properties deteriorate. Although a number of disease-modifying drugs to treat joint inflammation are available, data on the ability of these drugs to prevent fragility fractures are limited. Thus, specific treatment of osteoporosis should be considered in patients with RA and an associated increased risk of fragility fractures.

Keywords: bone mineral density; fractures; osteoporosis; pathophysiology; rheumatoid arthritis; sarcopenia.

Figure 1

Multinucleated bone resorbing osteoclasts (black arrows), histological section of a mouse humerus stained with tartrate-resistant acid phosphatase (TRAP) and toluidine blue. Original magnification: 400×.

Figure 2

A model of the pathophysiology of osteoporotic fractures in rheumatoid arthritis.