Lithium promotes better bone healing

Researchers at The Hospital for Sick Children (SickKids) have found a molecular pathway that plays a critical role in bone healing and have found that the drug lithium can improve the healing process.

This research is reported in the July 31 issue of PLoS Medicine. Delayed fracture healing can cause substantial disability and often requires additional surgical treatments. Finding a drug that could enhance bone healing has been a long-sought treatment that could improve fracture repair and substantially improve patient outcomes.

The signaling pathways regulating bone healing are beginning to be unraveled, and they provide clues into the pharmacologic management of bone repair.

The beta-catenin signaling pathway has emerged as a key regulator in embryonic skeletogenesis. However, its role in bone repair had been previously unknown. "At the beginning of the bone healing process we observed a significant increase in beta-catenin," said Dr. Benjamin Alman, senior scientist in Developmental & Stem Cell Biology at SickKids Research Institute, division head of Orthopaedic Surgery at SickKids, vice chair of the Department of Surgery at the University of Toronto and Canada Research Chair in Musculoskeletal Research. "We found that during healing of a tibia fracture in a mouse model beta-catenin was activated in both bone and cartilage formation during fracture repair." They found that treating mice with lithium activated beta-catenin in the healing fracture. However, healing was only enhanced when lithium treatment started after the fracture, meaning that while the level of beta-catenin has to be just right at the start of treatment, but after a few days, stimulates improved bone formation.

While this discovery has important implications for the development of therapeutics, the research team is now investigating other pathways involved in bone healing to see what role the pathways play in the process.

Other researchers on this paper were Yan Chen, Heather Whetstone, Alvin Lin, Puviindran Nadesan, Qingxia Wei and Raymond Poon all from SickKids.

This research was supported by Canadian Institutes of Health Research, the Canadian Research Chair Program, the Premier's Research Excellence Program of Ontario and SickKids Foundation.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system.