Potential role for therapies targeting DKK1, LRP5, and serotonin in the treatment of osteoporosis.

Osteoporosis is a common disorder in which diminished bone mass leads to progressive microarchitectural skeletal deterioration and increased fracture risk. Our understanding of both normal and pathologic bone biology continues to evolve, and with it our grasp of the highly coordinated relationships between primary bone cells (osteoblasts, osteoclasts, and osteocytes) and the complex molecular signals bone cells use to integrate signals derived from other organ systems, including the immune, hematopoietic, gastrointestinal, and central nervous systems. It is now clear that the Wnt signaling pathway is central to regulation of both skeletal modeling and remodeling. Herein, we discuss components of the Wnt signaling pathway (DKK1, an endogenous soluble inhibitor of Wnt signaling) and LRP5 (a plasma membrane-localized Wnt co-receptor) as potential future targets for osteoporosis therapy. Finally, we discuss the current controversial role for serotonin in skeletal metabolism, and the potential role of future therapies targeting serotonin for osteoporosis treatment.