In this lecture we want to explore the role of inflammation for development of bone damage in rheumatoid arthritis (RA) and illuminate if biologic DMARDs can prevent against RA bone loss mainly focusing on osteoporosis.
In RA bone involvement presents as joint erosions and periarticular and generalized osteoporosis. Generalized osteoporosis, an extraarticular manifestation of the RA disease, causes an increased risk of fractures and increases the burden of the RA disease. Inflammation is the driving mechanism behind bone damage in RA. In the absence of synovitis erosions do not occur, further markers of inflammation have been shown to be associated with development of both periarticular and generalized osteoporosis. These bone damage processes starts from the beginning of the disease. To suppress inflammation in RA may not only be important to prevent joint damage but also to avoid generalized inflammatory bone loss and may thereby reduce future fracture risk.
The field of osteoimmunology has over the last years increased our knowledge and given us insight into mechanisms involved in the bone damage processes in inflammatory joint disorders. In RA osteoclast recruitment and activation have been shown to be the dominant pathophysiological mechanisms involved in development of erosions and osteoporosis. These processes are driven by macrophage colony stimulating factors (MCSF) and receptor activator of NF-kB ligand (RANKL), and pro-osteoclastiogenic cytokines like e.g. tumor necrosis factor (TNF) and interleukins (IL)- 6 support this process. Targeted anti inflammatory treatment e.g. blocking the effect of TNF and IL-6 is thus a logical treatment principle to prevent bone damage in RA. The importance of RANKL in the development of bone damage including erosions in RA has been shown in a study using the osteoporosis drug denosumab. In this study the inhibition of RANKL by denosumab, a monoclonal antibody against RANKL, was shown to protect against development of erosions in RA, despite ongoing inflammation.
From the early beginning of the biologic treatment era in RA it has been known that anti TNF treatment is superior to synthetic DMARDs in reducing radiographic joint damage. Later on other biologic drugs with other modes of action have also shown to reduce the rate of radiographic joint damage (e.g. IL-6 inhibition, T-cell inhibition and B cell depletion). There are also data, however more scarce, that shows that biologic treatment also can reduce the development of generalized bone loss. These data highlights the importance of suppressing inflammatory mechanisms involved in bone damage to maintain bone health in RA to reduce fracture risk.
Disclosure of Interest None declared
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