New research in the United States challenges the current understanding of how bone fractures heal.
A team at Vanderbilt University Medical Center in Tennessee has discovered that fibrin, a protein that was thought to play a key role in fracture healing, is not required for this process at all. In fact, the breakdown of fibrin is essential for fracture repair.
Fibrin is involved in blood clotting, forming a mesh-like net that traps platelets to form a clot that stops bleeding.
Since fibrin is the main protein at the site of a fracture, it was thought to promote repair by providing a scaffold for the initial phase of new bone formation. However, the study published in the Journal of Clinical Investigation revealed that fracture repair was normal in mice missing the fibrin precursor fibrinogen.
What´s more, the team demonstrated that excess fibrin at the fracture site can actually impair healing. Mice that were unable to get rid of fibrin found it harder to form blood vessels and heal the fractured bone, while subsequent depletion of fibrinogen restored normal fracture repair processes.
The findings have implications for efforts to promote fracture repair, the researchers say.
“Many of the current pharmaceutical protocols are based on using fibrin to promote fracture healing,” explained Dr. Jonathan Schoenecker, assistant professor of Orthopaedic Surgery and Rehabilitation at Vanderbilt. “In certain instances it may help, but we´ve shown for sure that you don´t need it. Bone biology does not require fibrin to heal a fracture.”
The findings may also explain why obesity, diabetes, smoking and advanced age can impair fracture repair: they are all associated with impaired fibrin clearance.
This could mean that treatments to lower fibrinogen levels or increase the activity of enzymes that clear fibrin could improve bone healing, Dr. Schoenecker said.