Authors: O. Růžičková
Authors‘ workplace: Revmatologický ústav Praha
Published in: Čes. Revmatol., 20, 2012, No. 4, p. 181-197.
Category: Overview Reports


The skeleton forms the supporting structure of the muscular system, protects internal organs, is a site of hematopoiesis and participates in maintaining homeostasis of the human body. Bone tissue serves as storage of calcium and phosphorus that is able to participate in maintaining homeostasis if necessary. The skeleton is living tissue, which undergoes changes during the entire life. Remodeling, consisting of bone resorption and formation, thus facilitates adaptation of the skeleton to actual needs of the organism and repairs the microtrauma. Loss of bone mass accompanies several diseases such as chronic infectious diseases, rheumatoid arthritis, leukemia, postmenopausal osteoporosis, bone metastases etc. Bone remodeling, which includes bone resorption mediated by osteoclasts followed by deposition of new bone produced by osteoblasts, occurs on the surface of all bones according to actual needs. Bone remodeling is a process, which takes place in basic multicellular units at particular sites of the bone surface only. It is a continuous process, comprising bone resorption and formation, which enables regeneration of the bone while preserving its structure. Differentiation and activation of osteoblasts and osteoclasts is regulated by transcription factors, cytokines and growth factors, which are produced either locally by osseous cells or by systemic factors. RANKL/RANK interaction has a crucial role in the differentiation and survival of osteoclasts. OPG and RANKL have a key role in linking the function of osteoblasts and osteoclasts. Thus they have become a target of potential pharmacologic treatment of bone resorption. Upon binding of RANKL to RANK, a signal cascade regulating the differentiation and activation of osteoclasts is activated. RANKL-RANK stimulation is essential for the induction of osteoclastogenesis. Other signaling pathways may only modulate this dominant signaling cascade in a positive or negative way. OPG cannot affect the inflammatory activity of the disease. However, it can prevent the development of erosions and joint destruction. The effect of OPG is associated with the regulation of bone turnover. Bone remodeling and bone loss are controlled by the RANKL-RANK-OPG axis. RANKL is also produced by T cells as a response to antigenic stimulus. These T cells can also participate in the development and activation of osteoclasts. Thus, immune cells take part in bone metabolism both in health and the presence of inflammatory or autoimmune diseases such as rheumatoid arthritis. The development of denosumab, a human monoclonal antibody against RANKL, is a new, highly effective approach in the prevention of fragile osteoporotic fractures, skeletal complications of tumorous diseases and bone erosions in rheumatoid arthritis. Blockade of RANKL/RANK signaling does not lead to an immune dysfunction. Inhibition of RANKL does not affect the inflammatory reactions mediated by T cells in rheumatoid arthritis.

Key words:
osteoporosis, rheumatoid arthritis, bone remodeling, RANK, RANKL, OPG, denosumab


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