Oct. 22, 2007
UI receives $7.5 million to study post-traumatic osteoarthritis
The University of Iowa has received a five-year, $7.5 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) to establish a Center of Research Translation (CORT) for post-traumatic osteoarthritis, which is the joint degeneration, pain and stiffness that develops after joint injury.
Although joint injuries -- including dislocations, ligament injuries and joint fractures -- are known to cause post-traumatic osteoarthritis (PTOA), the biological and mechanical processes that underlie development and progression of osteoarthritis following injury are not well understood.
This lack of understanding has seriously hampered progress toward preventing PTOA, according to Joseph Buckwalter, M.D., the Dr. Arthur A. Steindler Chair in Orthopaedic Surgery and professor and head of orthopaedics and rehabilitation at the UI Roy J. and Lucille A. Carver College of Medicine. Buckwalter is principal investigator (PI) of the study.
"In the past 20 or 30 years, despite the fact that surgical techniques and imaging techniques have improved, the risk of developing arthritis after joint injury has not changed noticeably," Buckwalter said. "We haven't made more progress because we don't have a fundamental understanding of how PTOA develops. The goal of this grant is to discover the basic mechanisms that lead to PTOA and target those mechanisms to prevent the development and progression of the disease."
PTOA accounts for about 12 percent of all osteoarthritis, which itself is among the most common causes of pain, disability and economic loss. PTOA often occurs after joint injuries from motor vehicle accidents, falls, work-related accidents and sports injuries, and the risk of developing PTOA ranges from about 20 to 50 percent following common joint injuries.
A recent UI study conducted by Buckwalter and colleagues suggests that around six million Americans have PTOA and that the condition annually costs about $3 billion in direct medical costs and nearly $9 billion in indirect costs, including lost wages.
The central theme of the UI studies is that joint injuries initiates a sequence of biologic and, in some instances, mechanical events that lead to PTOA, and interventions that block or minimize these events will form the basis of new and improved treatments for injured joints.
"When a joint is injured, a number of cells are killed right away by the injury itself, just like a heart attack or stroke. But it is actually the propagation of damage over the first few days -- and especially in the critical first hours -- that we think is really important, and that seems to be the time to intervene if we want to prevent PTOA," Buckwalter said.
The UI researchers, led by Buckwalter and co-PI Thomas Brown, Ph.D., the Richard and Janice Johnston Professor of Orthopaedic Biomechanics, UI professor of orthopaedics and rehabilitation, and director of the UI orthopaedic biomechanics laboratory, will investigate how joint injuries propagate and develop new methods to assess joint injuries, prevent PTOA and promote joint healing. The collaborative, translational research will capitalize on UI strengths in cartilage and matrix biology, joint biomechanics, imaging, and clinical studies of PTOA.
"If we can discover the basic mechanisms that lead to PTOA and discover ways to prevent the development of osteoarthritis following a joint injury, we will most likely be able to stop other forms of osteoarthritis," Buckwalter said. "So our research has implications for everyone with this debilitating condition."
The CORT award will support four research projects:
-- Buckwalter and James Martin, Ph.D., research scientist, will lead a basic science project exploring how cells within a joint respond to injury and investigating the mechanisms by which an injury releases molecules that cause further damage. A better understanding of these biologic processes may help researchers devise interventions to prevent or alleviate PTOA.
-- Todd McKinley, M.D., associate professor of orthopaedics and rehabilitation, will lead a second basic science study also investigating the mechanisms of joint damage. His group will focus on the whole joint and will examine the interplay between damage caused by the initial injury and the subsequent, repetitive damage caused by abnormal stresses on the damaged, unstable joint. The team also will investigate whether certain biologically active molecules can be used to arrest the propagation of joint damage.
-- Douglas Pedersen, Ph.D., research engineer in the UI orthopaedic biomechanics laboratory, and Ned Amendola, M.D., professor of orthopaedics and rehabilitation, will conduct a project with both clinical and basic science components looking for biologic markers of joint injury and investigating the use of a new magnetic resonance imaging (MRI) technology to assess the severity of cartilage damage. The study will focus on joint injuries, like anterior cruciate ligament tears, that do not involve fractures.
-- Larry Marsh, M.D., professor of orthopaedics and rehabilitation, and Donald Anderson, Ph.D., associate research engineer, will lead a multi-center, clinical research project developing new strategies to quantify the severity of joint injuries that involve fractures at the joint surfaces. The UI team will collaborate with clinicians at the University of North Carolina, the University of New Mexico and the University of Virginia. Being able to quantify the severity of injury will help researchers determine which injuries are most likely to lead to PTOA and allow clinicians to assess the effectiveness of treatments.
The CORT grant also funds administrative/biostatistics, biomechanics/imaging, and tissue/experimental model activities that facilitate and support the translational research projects.
To date, NIAMS has awarded seven CORT grants, including the UI grant. These grants support multidisciplinary, translational approaches that combine basic and clinical research to help translate basic discoveries into new drugs, treatments and diagnostics for specific diseases.
STORY SOURCE: University of Iowa Health Science Relations, 5135 Westlawn, Iowa City, Iowa 52242-1178