ReviewInflammatory signaling induced bone loss
Introduction
A broad spectrum of inflammatory disorders have the capacity to target the skeleton and to de-regulate the processes of physiological bone remodeling. This review will focus on the systemic inflammatory rheumatologic disorders, which target articular and periarticular bone tissues. Many of these disorders also affect extra-articular tissues and organs, and in addition, have the capacity to produce systemic bone loss and increased risk of osteoporotic fractures. The articular inflammation and joint damage, as well as the generalized bone loss and additional systemic extra-articular manifestations, have a profound adverse effect on the quality of life and functional capacity of the affected individuals. Attention will focus on rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and the seronegative spondyloarthropathies (SpAs), which include ankylosing spondylitis (AS), reactive arthritis (formerly designated as Reiter's syndrome), and the arthritis of inflammatory bowel disease, juvenile onset-spondyloarthropathy and psoriatic arthritis. The discussion will principally focus on RA, which is a prototypical model of an inflammatory disorder that de-regulates bone remodeling, but also will review the other forms of inflammatory joint disease to highlight the differential effects of inflammation on bone remodeling in these conditions.
Section snippets
Structural organization of periarticular bone
To understand the articular and periarticular bone pathologies in the rheumatic diseases, it is important to appreciate the unique organizational features of the different joints. The joints can be divided into three categories based on their anatomic features [1]. They include the highly mobile diarthrodial joints, which are lined by a specialized synovial lining, e.g., the knee, wrist and small joints of the hands and feet; the amphiarthroses in which the adjacent bones are separated by
Rheumatoid arthritis
RA is a systemic inflammatory disorder that is characterized by a symmetrical destructive polyarthritis. The etiology of RA is unknown, but both genetic and environmental factors are involved in its pathogenesis [7], [8]. The hallmark of RA is the development of a chronic inflammatory polyarthritis that targets the synovial lining of diarthrodial joints. The earliest changes involve the proliferation of the synovial lining cells, consisting of a population of macrophage-like cells (A cells) and
Systemic lupus erythematosus
SLE is a systemic autoimmune disease characterized by loss of tolerance to self antigens that results in aberrant T and B cell activation and the generation of high affinity autoantibodies directed against host tissues leading to organ damage and dysfunction [71]. Symmetrical polyarthritis affecting diarthrodial joints is a characteristic feature of SLE, and the arthritis may be a significant contributor to the disease morbidity. Similar to RA the synovial lining undergoes proliferation and
Seronegative spondyloarthropathies
As described in the Introduction, the SpAs are a heterogeneous group of inflammatory disorders that exhibit articular and periarticular features that differ from RA. They are classified as seronegative forms of arthritis based on the absence of rheumatoid factors and ACPAs that are associated with RA. The genetic factors, particularly involvement of the HLA-B27 class I major histocompatibility (MHC) gene, differ from the genetic associations in RA, and in general, the SpAs do not exhibit
Conclusion
In conclusion, the rheumatic joint diseases share in common the capacity to produce a chronic synovial inflammatory reaction that can lead to disabling joint pain and disruption of the integrity and functional properties of joint tissues. These conditions also can affect systemic bone remodeling leading to progressive bone loss and increased risk of fracture. The de-regulated periarticular and systemic bone remodeling can be attributed to the capacity of the inflamed synovial, and in the case
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