New insights in the mechanism of bone loss in arthritis.
In chronic arthritis synovial inflammation is usually accompanied by bone erosion. Due to resulting structural damage, bone erosion is major reason for disability of RA patients. Thus, drug therapy in arthritis is not only focussed on the control of synovial inflammation but also on preserving bone from structural damage. Bone erosion in arthritis is a consequence of synovial osteoclast formation. Therapeutic approaches, which interfere with synovial osteoclastogenesis and/or osteoclast activation, are therefore of great interest. This review describes the pathomechanism of arthritic bone erosion, describes its cellular and molecular players and gives insights in current therapeutic tools to inhibit this process. Effects of blockade of tumor necrosis factor, interleukin-1 and receptor activator of NF-kB ligand are discussed. Arthritis and bone loss are two related conditions but they are not necessarily linked to each other. Thus, in case of short-lasting and self-limited disease, structural damage is highly unusual. One of the most intriguing examples is viral arthritis, which as in case of parvovirus infection is a polyarticular disease closely mimicking rheumatoid arthritis. However, parvoviral arthritis is always a self-limited condition and resolves without any structural damage. In contrast, chronic forms of arthritis, such as psoriatic arthritis or rheumatoid arthritis (RA) are usually destructive and lead to alteration of joint structure and functional impairment.
Schett
Georg
G
Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Vienna, Austria. georg.schett@meduniwien.ac.at
Smolen
Josef S
JS
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D001842:Bone and Bones / Q000473:pathology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
D018501:Antirheumatic Agents; D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human