The control of fracture healing and its therapeutic targeting: improving upon nature

J Cell Biochem. 2010 Feb 1;109(2):302-11. doi: 10.1002/jcb.22418.

Abstract

Fracture repair is a complex process involving timed cellular recruitment, gene expression, and synthesis of compounds that regenerate native tissue to restore the mechanical integrity, and thus function of injured bone. While the majority of fractures heal without complication, this takes time and a subset of patients ( approximately 10%) experience healing delays, extending their morbidity and treatment costs. Consequently, there is a need for efficacious therapeutics for the intervention of fracture healing. Recent studies into the molecular control of fracture repair and advances in the understanding of the skeleton as a whole have resulted in the identification of numerous novel targets and compounds for such intervention. These include traditional agents such bone morphogenetic proteins and other growth factors, but also relatively newer compounds such as parathyroid hormone and modulators of the Wnt signaling pathway. These agents, along with others, are discussed in the current article in terms of their investigative status and potential for clinical implementation. Hopefully, these agents, as well as others yet to be discovered, will demonstrate sufficient clinical utility for successful intervention of fracture healing. This may have significant implications for the duration of morbidity and costs associated with traumatic bone fractures.

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Bone Morphogenetic Proteins / therapeutic use
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Fracture Healing*
  • Fractures, Bone* / metabolism
  • Fractures, Bone* / pathology
  • Fractures, Bone* / therapy
  • Gene Expression Regulation
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / therapeutic use
  • Mice
  • Neovascularization, Physiologic
  • Parathyroid Hormone / genetics
  • Parathyroid Hormone / metabolism*
  • Parathyroid Hormone / therapeutic use
  • Rats
  • Signal Transduction / drug effects
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • Intercellular Signaling Peptides and Proteins
  • Parathyroid Hormone
  • Wnt Proteins