Osteoimmunology: Major and Costimulatory Pathway Expression Associated with Chronic Inflammatory Induced Bone Loss

Abstract

The field of osteoimmunology has emerged in response to the range of evidences demonstrating the close interrelationship between the immune system and bone metabolism. This is pertinent to immune-mediated diseases, such as rheumatoid arthritis and periodontal disease, where there are chronic inflammation and local bone erosion. Periprosthetic osteolysis is another example of chronic inflammation with associated osteolysis. This may also involve immune mediation when occurring in a patient with rheumatoid arthritis (RA). Similarities in the regulation and mechanisms of bone loss are likely to be related to the inflammatory cytokines expressed in these diseases. This review highlights the role of immune-related factors influencing bone loss particularly in diseases of chronic inflammation where there is associated localized bone loss. The importance of the balance of the RANKL-RANK-OPG axis is discussed as well as the more recently appreciated role that receptors and adaptor proteins involved in the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway play. Although animal models are briefly discussed, the focus of this review is on the expression of ITAM associated molecules in relation to inflammation induced localized bone loss in RA, chronic periodontitis, and periprosthetic osteolysis, with an emphasis on the soluble and membrane bound factor osteoclast-associated receptor (OSCAR).

Assessment of local and systemic 25-hydroxy-vitamin D, RANKL, OPG, and TNF levels in patients with rheumatoid arthritis and periodontitis

“…Our results are partly compatible with available literature. RANKL/OPG ratio has been associated with bone destruction (5,20,36,38). Supporting this, van Tuyl et al suggested that RANKL/ OPG and collagen terminal I and II (CTX) were strong predictors of rapid and persistent disease activity in RA (39).…”

Increased risk of fracture in patients with bipolar disorder: a nationwide cohort study

“…Although proinflammatory cytokines, such as IL-1, IL-6, and TNF-a, are critical in bone metabolism, these cytokines have also been attributed to the pathogenesis of osteoporosis and an increased risk of fracture [18]. Studies have shown that chronic inflammation can mediate bone loss through the disturbance of the receptor activator of nuclear factor j-B ligand (RANKL)-RANK-osteoprotegerin (OPG) axis, an essential regulator in bone metabolism [19,20]. Except for inflammatory autoimmune diseases, such as RA and systemic lupus erythematosus [21], an increased risk of fracture has been reported for such medical conditions as diabetes mellitus and chronic kidney disease [22,23].…”

Virulence factors associated withAggregatibacter actinomycetemcomitansand their role in promoting periodontal diseases

“…directly in the periodontium. 22,23 Clinical studies have shown a high expression of these markers in patients with periodontal disease. 21 These cytokines may induce bone resorption, affecting the production of essential osteoclast differentiation and the resulting bone destruction.…”

“…The stimulatory factors regulating this process are cytokines such as interleukin-1 (IL-1), macrophage colony-stimulating factor (MCSF), monocytes and T cells. 22,24 The treatment of periodontal disease is based on virulence factors, the microorganisms that are established in the processes of health and disease; therefore, the treatments must aim to control these microorganisms. 4,8,9 It is necessary to understand the role of bacterial biofilm in the etiology of periodontal diseases, as the severity and progression of these diseases are determined in large part by factors related to the host's response.…”