Orthopedics and rehabilitation investigators receive major grants

The Department of Orthopedics and Rehabilitation was recently awarded two large grants from the Department of Defense (DOD).

Joseph Buckwalter IV, MD

A $10 million Focused Program Award from the DOD Congressionally Directed Medical Research Program will allow investigators in the department to advance their investigations designed to prevent, delay, or mitigate post-traumatic osteoarthritis (PTOA) after intra-articular fractures (IAFs) and other joint injuries.

Joseph A. Buckwalter, MS, MD, a world-renowned expert in PTOA, is the principal investigator of the study, titled, “Translating metabolic responses to mechanical insult into early interventions to prevent PTOA.”

J. Lawrence Marsh, MD, chair and DEO of orthopedics and rehabilitation, says, “This is a tremendous achievement in basic and translational science for our department and provides the opportunity to make a difference for millions of patients through research into mechanisms and treatments of PTOA.”

J. Lawrence Marsh, MD

The need to develop improved treatment of joint fractures is clear. IAFs often lead to chronic pain and decreased function and they typically occur in young active people or in military personnel. Despite current optimal treatment, many of these injuries result in crippling arthritis that compromises quality of life and in young patients there are few reconstructive options. PTOA is responsible for more than six percent of all severe osteoarthritis and the financial impact in the United States exceeds $15 billion. It is the most common cause of permanent disability in military personnel and causes impairment as severe as advanced kidney and heart disease.

In the grant application, Buckwalter notes, “For over 20 years, our group has been conducting clinical and basic scientific studies of mechanical and biologic pathways that lead to PTOA. Our ultimate goal is to prevent this crippling disease.” The program will include four synergistic projects:

Project 1: Small-scale early phase clinical trial of amobarbital to reduce PTOA risk in tibial pilon fractures
Principal investigators: J. Lawrence Marsh, MD, and James C. Torner, PhD

Project 2: Integrating pathomechanical PTOA risk into clinical decision-making following IAF
Principal investigators: Donald D. Anderson, PhD, and Jason M. Wilken, MPT, PhD

Project 3: Supplementing joint lubrication as an adjunct to amobarbital treatment
Principal investigators: James A. Martin, PhD, and Aliasger Salem, PhD

Project 4: Correlation of cartilage mechanics with chondrocyte mitochondrial dysfunction targeted by amobarbital
Principal investigators: Jessica E. Goetz, PhD, and Mitchell C. Coleman, PhD

A second award from the DOD will allow for a complimentary randomized prospective investigation of a biologic intervention to help prevent articular cartilage loss in patients with tibial pilon fractures. With current treatment methods these severe injuries have a high risk for PTOA.

This $3 million dollar award supports a collaboration among the University of Indiana, the University of Iowa, and the METRC consortium and will bring almost $1 million dollars to the University of Iowa.

The title of the program is, “Preventing post-traumatic osteoarthritis in pilon fractures with intra-articular amobarbital: A prospective randomized controlled clinical trial.” Principal investigators are Todd O. McKinley, MD (Indiana University), and James A. Martin, PhD (University of Iowa); and UI investigators are J. Lawrence Marsh, MD, Joseph A. Buckwalter, MS, MD, Donald D. Anderson, PhD, Mitchell C. Coleman, PhD, James C. Torner, PhD, Michael Willey, MD, and Aliasger Salem, PhD.

Congratulations to the investigators and the department on receiving these funding awards.

Above: Con-focal microscope image of the fractured articular cartilage of a human ankle joint. Marked by arrows, the edge of the fracture shows dead cartilage cells (red dots) and living cells (green dots). This severe joint injury initially killed few cells next to the fracture, but in the 48 hours following the injury many more cells died. UI researchers have provided the first evidence that cartilage cell death and arthritis caused by joint fractures can be prevented using safe, readily available drugs.