Inflammatory disorders such as rheumatoid arthritis (RA), may have profound effects on skeletal homeostasis. In contrast to physiologic remodeling in which mechanical influences and/or systemic endocrine hormones initiate the remodeling process, in disorders such as RA the recruitment of macrophage lineage cells to sites of inflammation and the action of local osteoclastogenic cytokines associated with the inflammatory process initiate the remodeling process. In both physiologic and pathologic remodeling, osteoclasts appear to be the principal cell type responsible for the bone resorption. In addition, many of the same cytokines and mediators are involved in physiologic and pathologic bone remodeling. These observations have important implications with respect to the development of therapeutic strategies to prevent bone loss in inflammatory conditions.