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Why Some Injured Muscle Grows Bone: Substance P


It’s one of the mysteries of medicine: why do some injured muscles grow bone? Now researchers at Northwestern University Feinberg School of Medicine and the Perelman School of Medicine at the University of Pennsylvania have found an answer, a neuropeptide called substance P.

Why do some muscles think they’re bones?

After injuring a muscle in an accident or undergoing surgery, there is a chance you will experience traumatic heterotopic ossification, a complication in which muscle tissue forms bone. Following joint replacement in a lower limb, for example, a recent report in the Journal of Bone and Joint Surgery noted that heterotopic ossification occurs in 3 to 90 percent of cases.

For some people who develop heterotopic ossification, there is little or no pain or discomfort, but for others, it can be “very uncomfortable, and there is no way to make it go away,” according to Jack Kessler, MD, the new study’s senior author as well as chair of neurology at Northwestern’s Feinberg School and a neurologist at Northwestern Memorial Hospital.

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However, new research has identified substance P, a neuropeptide in the brain, as the trigger behind the abnormal bone growth. With this discovery, researchers now have a way to potentially prevent and treat this condition.

The investigative team, led by Lixin Kan, research associate professor at Feinberg and the lead author, discovered that substance P levels increase significantly in newly injured tissue of patients who have heterotopic ossification along with a rarer, debilitating genetic disease called fibrodysplasia ossificans progressive (FOP). In people with FOP, their connective tissue—the tissue within which muscle and nerve tissue are embedded—begins to turn into bone.

The Northwestern team found that eliminating substance P in an animal model prevented the abnormal growth of bone. According to Frederick Kaplan, a co-author of the study and the Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine at Penn’s Perelman School, their finding identifies a common factor responsible for the formation of “nearly all forms of heterotopic ossification including brain and spinal cord injury, peripheral nerve injury, athletic injury, total hip replacement and FOP.”

Now that researchers have found substance P to be a reason why some injured muscles grow bone, it “gives us a way to develop a therapy to potentially treat it,” noted Kessler. Such therapy could be welcomed by the hundreds of thousands of people who experience this abnormal bone growth.

Board TN et al. Journal of Bone and Joint Surgery, British 2007 Apr; 89(4): 434-40
Northwestern University