Role of the immune system in postmenopausal bone loss

Postmenopausal osteoporosis stems from estrogen deficiency. The mechanisms by which estrogen deficiency drives bone destruction are complex and poorly understood. Recent findings from animal models suggest that postmenopausal bone loss may stem in large measure from a pathologic upregulation of the adaptive immune response. While the role of activated T cells in the bone loss driven by inflammatory conditions such as rheumatoid arthritis has been well documented, only recently has the role of T cells in the bone destruction associated with estrogen deficiency begun to be appreciated. In vivo and in vitro models of postmenopausal osteoporosis demonstrate that the activation and expansion of tumor necrosis factor-a producing T cells is a key step in estrogen deficiency driven bone loss and is regulated by multiple interacting cytokines including transforming growth factor-b, interleukin-7, and interferon-g, as well as by the process of antigen presentation. This paper presents recent findings pertaining to this new view of postmenopausal osteoporosis.