Rheumatoid arthritis (RA) is a chronic, inflammatory and destructive joint disorder with progressive course, which results in functional limitation, physical disability as well as in extra-articular and systemic manifestations. Besides the soft tissue changes associated with synovitis, bone remodelling is also altered by local and systemic effects of inflammatory process. Activated osteoclasts are responsible for majority of bone resorption followed by focal erosions, juxta-articular and diffuse osteoporosis. Osteoresorption is up-regulated by bone-resorbing factors, which do not affect differentiation and activation of osteoclasts directly, but rather affect osteoblast activation. Osteoblasts than produce molecules regulating osteoclastogenesis – osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL). The balance between resorption and formation of bone is regulated by relative concentrations of these molecules in the local bone microenvironment. RANKL binds to RANK on the surface of osteoclast precursors and after growth factor M-CSF contribution causes osteoclasts to differentiate and become activated. Osteoprotegerin modulates osteoclastogenesis by competitive inhibition ofRANK/RANKLinteraction, which induces inhibition of osteoclast activation and subsequently reduces their survival. This process is regulated by inflamed synovial cells (T cells, macrophages and fibroblast like cells). Osteoclastogenesis is associated with osteoblastogenesis through three key molecules RANKL, RANK and OPG. Increased RANKL/OPG ratio induces osteoresorption and results in bone destruction. One of the possible therapeutic targets to reduce observed bone destruction is RANKL inhibition by natural inhibitor – OPG.

        Key words: rheumatoid arthritis, osteoprotegerin, RANK, RANKL, bone resorption, osteoclastogenesis