The roles of prostanoids, leukotrienes, and platelet-activating factor in bone metabolism and disease

The production of a variety of lipid mediators is enhanced in bone-resorptive diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontitis. Prostaglandin E2 (PGE2) is one of the most notable lipid mediators of bone remodeling, and has been linked clinically to many bone-resorptive diseases. In vitro studies with bone cell cultures have demonstrated that the bone-resorptive activity of PGE2, which is mediated by receptor activator of NF-κB ligand (RANKL), is key for the induction of osteoclast formation. Furthermore, interleukin (IL)-1- and IL-6-stimulated bone resorption involves PGE2 production. In addition to its bone-resorptive effects, PGE2 promotes bone formation in vitro by stimulating osteoblastic proliferation and differentiation. The multifaceted nature of PGE2 makes it difficult to discern its role during bone remodeling. Leukotrienes (LTs), and particularly LTB4, have also been implicated in bone remodeling and disease—specifically in rheumatoid arthritis. Moreover, recent studies from our laboratory have shown that platelet-activating factor (PAF) receptor-deficient mice develop only mild osteoporosis. Osteoclast survival in these mice is shortened and osteoclastic bone resorption is impaired. This review article focuses on these families of lipids and their function during bone metabolism and disease.