When a study demolishes a century-old belief about how fractured bones heal, it is labeled a “breakthrough.”
That is what researchers at Vanderbilt University have achieved in their discovery that fibrin is not essential to bone healing—as everyone once thought. It turns out that it is the breakdown and clearance of fibrin that is essential to the healing process. Tiffany Parnell wrote in MDNews that the Vanderbilt study “alters a century-old belief about bone fracture healing.”
As Parnell explained, when a bone is broken and normal vasculature is disrupted, the enzyme thrombin converts fibrinogen to fibrin. Fibrin is an insoluble protein that forms a fiber mesh at the site of the injury. Because doctors found fibrin present at every site of a bone fracture they believed, for a hundred years, that the fibrin was forming the scaffold for the bone to heal.
Not so, writes Jonathan Schoenecker, M.D., Ph.D., assistant professor of Orthopaedics, Pharmacology, Pathology and Pediatrics at the Vanderbilt Center for Bone Biology and senior author of the Journal of Clinical Investigation-published study.
It all began when Schoenecker received a grant to demonstrate the mechanism by which fibrin heals bone fractures. Orthopedic surgeons are concerned about their patients getting deep vein thrombosis. To prevent it they often prescribe anticoagulants. The researchers suspected that anticoagulant use may interfere with fibrin production.
“There’s a lot of data that suggests that the use of anticoagulants has a negative effect on healing tissue, ” Schoenecker said. “Going into this project, the assumption was that the reason why patients were having a hard time healing their fractures or wounds was because we were reducing the amount of fibrin that was laid down. We thought that the template [for healing] wasn’t there.”
Schoenecker and his team of researchers from the Schoenecker Lab at Monroe Carell Jr. Children’s Hospital at Vanderbilt hoped to determine how much fibrin was necessary to heal a fracture. Their goal was to find the dosage at which anticoagulants are effective at preventing thrombosis but do not deplete fibrin levels to the point that normal wound healing would be disrupted.
According to Parnell, researchers had hypothesized that fibrin was indispensable for fracture repair and that impaired fibrin clearance due to disruption of the fibrinolytic system contributed to healing complications. They tested their theory on three groups of mice and were astounded when the fractures on mice lacking fibrinogen healed normally. “It took six months for us to believe the research, ” Schoenecker said.
“If anticoagulants do have an effect on fracture healing, it sure isn’t because of fibrin, ” Schoenecker said. “[The study] completely opens up what we can do pharmacologically because we now know that those two things aren’t tied together. That’s been the fear in orthopedics for a really long time—that the anticoagulant use would drop the amount of fibrin, which makes it so the template isn’t there for healing. That’s where this work is really a breakthrough.”
