Bone and the immune system

Abstract

The mechanisms that control physiological and pathological bone mass and turnover have been extensively investigated over the past several decades. One surprising discovery that emerged during this journey is the existence of an immuno-skeletal interface (ISI), a centralization of shared cells and cytokine effectors serving dual, but separate, functions within both the immune and skeletal systems. The existence of this ISI has profound consequences for normal bone turnover and homeostasis and also appears to be key to the etiologies of multiple diverse osteoporotic conditions relating to rheumatoid arthritis, periodontal infection, postmenopausal osteoporosis, hyperparathyroidism, HIV infection, and antiretroviral therapy. Although most ISI activities elucidated to date converge on the process of bone resorption, recent studies have identified unexpected anabolic roles of the ISI in bone formation. Specifically, the bone anabolic actions of parathyroid hormone and the pharmaceutical costimulation inhibitor CTLA4-Ig (abatacept) are mediated though mechanisms involving T-cells. This chapter documents some of the key discoveries in the field of osteoimmunology in the context of both physiological and pathological bone turnover.