title: Wnt signaling as a therapeutic target for bone diseases.
abstract: BACKGROUND
  There is a need to develop new bone anabolic agents because current bone regeneration regimens have limitations. The Wingless-type MMTV integration site (Wnt) pathway has emerged as a regulator of bone formation and regeneration.
  
  
  OBJECTIVE
  To review the molecular basis for Wnt pathway modulation and discuss strategies that target it and improve bone mass.
  
  
  METHODS
  Data in peer-reviewed reports and meeting abstracts are discussed.
  
  
  CONCLUSIONS
  Neutralizing inhibitors of Wnt signaling have emerged as promising strategies. Small-molecule inhibitors of glycogen synthase kinase 3beta increase bone mass, lower adiposity and reduce fracture risk. Neutralizing antibodies to Dickkopf 1, secreted Frizzled-related protein 1 and sclerostin produce similar outcomes in animal models. These drugs are exciting breakthroughs but are not without risks. The challenges include tissue-specific targeting and consequently, long-term safety.
authors.affiliation: Graduate Program in Microbiology, Immunology and Cancer Biology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Luke H
authors.initials: LH
authors.lastname: Hoeppner
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Secreto
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf