Background: Active military members regularly confront blast-related trauma and high-impact damage to their joints. And, away from combat theaters, high-demand training and motor vehicle accidents can sideline personnel in military units already struggling to maintain peak potential. Unfortunately, recovery from joint injury is often complicated by the rapid onset of osteoarthritis. When traumatic injury incites the eventual degeneration of a joint, doctors classify this as post-traumatic osteoarthritis (PTOA). Even seemingly minor injuries can develop into painful joint deterioration and failure in less than 2 years. Consequently, PTOA is the leading factor in forcing military personnel into limited duty status or even medical retirement. The goal of this project is to prevent or slow the development of PTOA, and thus extend the useful life of injured joints.

Our previously funded Department of Defense project focused on experimental treatment of PTOA in Yucatan minipigs, which were chosen as models because they are roughly the same weight as an adult human. In this innovative model, a pendulum was used to break the animal's ankle, which was then repaired using surgical techniques and instruments similar to those used at military and civilian hospitals. By using familiar medical routines, the successes of treatment in animal models afflicted with PTOA can be easily translated into methods for treating human patients.

Objective: Expanding upon the original research, our next experiments would test the potential effectiveness of mechanically unloading a joint on preventing the development of PTOA. Traditional "non-weight bearing" using crutches or a wheelchair reduces the amount of force passing through a joint; however, the bones in the joint still touch each other. In contrast, the newly proposed treatment will use a device called an external fixator, which is screwed to the bones on each side of the joint, to push the ends of the bones apart until a small gap exists. One experimental group would have the external fixator placed during the initial surgery to repair fractured ankles. A second group would be fixated 3 months later. In both cases, joints will be unloaded for 6 weeks. Fixators would then be removed, followed by a period of normal joint loading and motion. To conclude the study, the animals would be sacrificed, and their joints analyzed for development of PTOA. In particular, microscopic examination of the cartilage will evaluate the ability of cells to regenerate, replicate, and reestablish normal function -- providing a comprehensive assessment of this treatment for PTOA prevention.

Potential Benefits: The proposed work would be performed with animal modeling, but positive results could be applied to benefit human patients in the near future. This type of joint unloading already has anecdotally been shown to reduce pain and improve function in patients who could otherwise be treated only with joint replacement or joint fusion. And because the protocols and equipment are already available and in use in the medical community, universal implementation could stop PTOA in its tracks, before it even develops.

From a research perspective, this investigation of mechanical unloading on cartilage health would be among the first to allow direct investigation of the effects of unloading on regenerative cartilage. With an animal model, we will be able to determine whether tissue regenerating as a result of unloading is similar in structure and chemistry to normal cartilage -- or whether the process results in only diffuse, poorly organized soft tissue. Also, with direct access to the tissue, it will be possible to measure the degree to which cartilage cells either degrade or invigorate their surrounding tissue. The tissue-level information that will be gathered from this work, combined with foreseeable easy acceptance, should pave the way for a major clinical trial in human patients.

Military Benefit: If mechanical unloading early after injury can be proven to slow or prevent joint degeneration, it could fundamentally transform clinical care of joint injury in the military. Imagine a world where traumatic injury no longer automatically leads to debilitating or career-ending PTOA. Decreasing the early onset of PTOA among our troops translates to more returns to active duty and increased force retention. This proposed work has the potential to dramatically improve individual patient outcomes and to decrease the support burden on the military by reducing the overall size of its community of medically disabled personnel.