Symposium Article
Structural Bone Changes in pondyloarthritis: Mechanisms Clinical Impact and Therapeutic Considerations

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Abstract

Spondyloarthritis (SpA) is an inflammatory disease of the spine, the peripheral joints and the entheses and shares some clinical features with rheumatoid arthritis (RA). Chronic inflammation of musculoskeletal structures leads to disease symptoms such as pain and stiffness and structural changes in the bone tissue. Furthermore, therapies for SpA are based on those for RA, which attempt to inhibit synovial inflammation that leads to retardation or even arrest of structural damage. However, in SpA, the bone tissue directly exposed to inflammation (osteitis) is the trabecular bone of the vertebrae, but not the cortical bone surface as in RA (synovitis). Therefore, the success of treatment strategies for structural changes in RA may not be appropriate for SpA. In this article, the authors discuss the pathophysiology of structural damage in SpA and concepts for the preservation of the physiologic bone architecture in patients with SpA.

Section snippets

THE RELATION OF INFLAMMATION TO STRUCTURAL DAMAGE

“Low inflammation leads to low structural damage” is the concept we have learned from RA. At first sight, this concept holds true for SpA. A tighter therapeutic regimen with continuous use of nonsteroidal anti-inflammatory drugs is more effective in retarding structural progression in SpA than a more “laissez-faire” strategy that allows nonsteroidal anti-inflammatory drugs only on demand.1 This concept, however, is challenged by the failure of all 3 approved tumor necrosis factor (TNF)

LYMPHOCYTES AND THE ROLE OF OSTEOCLASTS IN INFLAMMATION

Accumulation of lymphocytes in the bone marrow is likely to be the reason for the generation of osteoclasts, because activated lymphocytes are the primary source of receptor activator of nuclear factor kappa-B ligand, a molecule that drives osteoclast differentiation. Vertebral osteoporosis and resorption of trabecular bone thus seems to be the direct consequence of inflammation. This notion highlights a major difference between SpA and RA: in SpA, the bone tissue directly exposed to

ANABOLIC CHANGES AND THE PATHOPHYSIOLOGY OF SPA

Anabolic changes leading to syndesmophyte formation and ankylosis in SpA are of particular interest in understanding the pathophysiology of the disease. Current concepts suggest that, in patients with SpA, both mechanical triggers (enthesial stress) and inflammatory triggers (enthesitis) lead to mesenchymal tissue responses associated with the formation of new bone that bridges the intervertebral spaces, the small facet joints of the spine and the sacroiliac joints. Formation of bony spurs

TREATMENT STRATEGIES

The recent data on DKK-1 and sclerostin suggest that Wnt activation may be a decisive step in the formation of ankylosis in patients with SpA. Blocking of Wnt signals could thus represent an interesting strategy to inhibit ankylosis; however, this strategy bears the risk of generalized bone loss and osteoporosis, because it would likely inhibit bone formation in general. Specific strategies to block periosteal bone formation without affecting trabecular bone remain to be determined. Such

CONCLUSION

In summary, syndesmophytes in SpA are based on the differentiation of periosteal bone lining cells into osteoblasts leading to the deposition of new bone. This process, which results in ankylosis, is triggered by factors that support the differentiation of mesenchymal cells into osteoblasts. Prostaglandins such as prostaglandin E2, Wnt proteins and BMPs seem to be key signals, are responsible for bony overgrowth in SpA and constitute promising targets to halt structural changes in SpA.

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This study was supported by the Deutsche Forschungsgemeinschaft (FG 661/TP4 and SPP1468-IMMUNOBONE), the Bundesministerium für Bildung und Forschung (BMBF; projects ANCYLOSS and IMMUNOPAIN) and the MASTERSWITCH, KINACEPT, IMI and ADIPOA projects of the European Union.

Presented at the annual research and education meeting of Spondyloarthritis Research and Treatment Network (SPARTAN), Houston, Texas, July 23–24, 2010.

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