A new paradigm in the treatment of osteoporosis: Wnt pathway proteins and their antagonists.

The need to develop novel drugs that stimulate bone formation and thereby elevate bone mass (anabolics), as opposed to preventing bone loss (anti-resorptives), has opened new research areas for therapeutic intervention in the treatment of osteoporosis. One of these areas is the Wnt/beta-catenin (canonical) pathway that plays an important role in regulating osteoblast proliferation and differentiation. Alterations in this pathway have been associated with bone disorders characterized by either low or high bone mass. However, as the Wnt/beta-catenin pathway is a ubiquitous mechanism not just exclusively involved in bone formation, targeting Wnts may be a challenge (eg, targeting Wnt activity may induce cancer). Nevertheless, specific pharmacological targets to influence bone formation have been identified in this pathway; these include the Wnt-lipoprotein receptor-related protein 5/6-frizzled complex and Wnt antagonists such as sclerostin. Since sclerostin expression is highly restricted to osteocytes, this specific target may be ideal for anabolic drug therapy.