July 11, 2008

Military grant spurs bone regrowth study

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Erika Mitchell, M.D.

Military grant spurs bone regrowth study

A Vanderbilt physician has won a $1.3 million grant from the U.S. military to try to figure out why disorganized bone cells may grow wildly into soft tissue following a fracture or amputation, instead of knitting together neatly.

The complication strikes wounded American soldiers at a rate much higher than civilians, leading to the three-year grant from the U.S. Army Medical Research and Materiel Command.

Erika Mitchell, M.D., assistant professor of Orthopaedic Trauma, hopes that learning what causes the excess bone growth will one day mean it can be turned off — or on, in cases where such growth is needed.

The condition, called heterotopic ossification, is evident on X-rays, appearing as a swirl of shadowy bone that forms around a fracture or stump within six to eight weeks. It can limit range of motion and cause problems with prosthetics.

Typically the condition occurs in 11 percent to 25 percent of patients who've experienced serious trauma, such as in auto accidents. Yet it's being seen in a staggering 63 percent of military casualties.

“That number is extremely high, and extremely problematic,” Mitchell said. “That's why the military is very interested. This bone growth can become so excessive that it needs to be removed. In the case of amputation stumps, the stumps have to get shorter. That causes prostheses problems and requires multiple surgeries, which we'd like to avoid.

“At the same time, if we could bottle this extra production of bone, it would be very nice because we have plenty of bones that don't heal. If we understand how this excessive bone growth occurs, maybe we could better understand how we can create bone growth when needed.”

Researchers aren't sure why, but several studies indicate a link between serious head trauma, a common injury on battlegrounds, and heterotopic bone formation. Yet at the same time, it doesn't occur in every patient with head trauma and a fracture. That leads Mitchell to suspect that some people have a genetic predisposition toward the condition.

The grant, part of the Defense Department's Orthopaedic Trauma Research Program, is a cooperative venture between Vanderbilt's Division of Orthopaedic Trauma and Division of Trauma.

“This round of funding really marks a shift in the Defense Department's request for proposals,” said John Morris Jr., M.D., director of the Division of Trauma & Surgical Critical Care. “The Defense Department is actively looking to engage the civilian clinical scientific community in practical problems resulting from this (Middle East) conflict.”

Mitchell and her team will examine clinical information gathered on patients to find those with heterotopic ossification. They'll divide those patients based on categories such as the severity of their injuries, medications they were on and their overall physical condition at the time of their injury. Then Mitchell will explore their genetic data, hoping to identify underlying gene markers that can be linked to the condition.

It's a promising premise, Morris said.

“This study looks at the area that is just coming into focus — the role of the genome in response to traumatic injury,” he said. “The hope is we are going to find multiple pathways where small variations in the genome alter outcome following trauma.”

The multidisciplinary research team also includes Judy Jenkins, R.N.; Patrick Norris, M.D.; Jeffrey Canter, Ph.D.; and David Tabor, M.D.