Wnt signaling and potential applications in bone diseases

Curr Drug Targets. 2008 Jul;9(7):581-90. doi: 10.2174/138945008784911778.

Abstract

In the United States, it is estimated that $10-15 billion is spent annually for the treatment of osteoporotic fracture. The worldwide annual incidence of osteoporotic hip fracture exceeds 1.7 million cases. Bone loss leading to osteoporosis and osteoporotic fractures are caused by an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption and numerous factors have been implicated in the development of osteoporosis. The prevention and treatment of osteoporosis traditionally involves the use of anti-resorptive agents, which target osteoclast function, but do not lead to a significant increase in bone mass and therefore only partially reduce risk of fractures. For these reasons, the search for anabolic agents, which target osteoblast function, represents an urgent medical need. Genetic studies have firmly established a link between bone mass in humans and Wnt signaling. Multiple genetic and pharmacological manipulations of Wnt signaling in mice have since then confirmed the central role of this pathway in regulating bone formation. The existence of many potential pharmacological targets in this pathway makes it attractive for bone anabolic drug discovery.

Publication types

  • Review

MeSH terms

  • Anabolic Agents / pharmacology
  • Anabolic Agents / therapeutic use
  • Animals
  • Bone Diseases / drug therapy
  • Bone Diseases / epidemiology
  • Bone Diseases / physiopathology*
  • Bone and Bones / metabolism
  • Drug Delivery Systems
  • Fractures, Bone / etiology
  • Fractures, Bone / prevention & control
  • Humans
  • Mice
  • Osteoporosis / drug therapy
  • Osteoporosis / epidemiology
  • Osteoporosis / physiopathology
  • Signal Transduction*
  • United States / epidemiology
  • Wnt Proteins / metabolism*

Substances

  • Anabolic Agents
  • Wnt Proteins