[Pathogenesis of osteoporosis in rheumatoid arthritis]

Osteoporosis is a major clinical problem in rheumatoid arthritis. Patients with rheumatoid arthritis frequently not only present with juxta articular osteopenia and bone erosions but also with generalized axial and appendicular osteoporosis at sites distant from inflamed joints. The pathogenesis of bone loss in rheumatoid arthritis is multifactorial; disease activity certainly is a major determinant of bone mass. Further pathogenetic factors include effects of anti-inflammatory therapies (in particular glucocorticoids), reduced mobility, estrogen and/or androgen deficiency. Recently, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG), a decoy receptor for receptor activator of nuclear factor kappa B ligand, were identified as central regulators of osteoclast recruitment and activation. Osteoprotegerin and receptor activator of nuclear factor kappa B ligand production is modulated by several cytokines, growth factors and hormones. In rheumatoid synovium both fibroblasts and activated T cells express receptor activator of nuclear factor kappa B ligand and thereby promote osteoclast recruitment and activation. Thus, osteoprotegerin and receptor activator of nuclear factor kappa B ligand appear to represent important molecular links between the immune system and bone metabolism in rheumatoid arthritis.