Mechanisms and Treatments of Heterotopic Ossification Following Spinal Cord Injuries
Abstract
One of the frequent complications of spinal cord injuries is the formation of bones outside of the skeleton, particularly around joints such as the knee, hip, elbow, or shoulder. These bone masses growing outside of the skeleton are called heterotopic ossifications. They appear in 20%-25% of civilian patients suffering spinal cord injuries and can be found in up to 60% of Soldiers victim of battlefield injuries affecting the spinal cord or the brain. These heterotopic ossifications appear a few weeks after the spinal cord injury, usually with inflammatory pain, and grow over a few months to become so large (up to 2 kg or 4 pounds) that they block muscles and joints. As a result, patients cannot bend their joints as they are entrapped in these hard mineralized heterotopic bones. The consequences are dramatic for the well-being and rehabilitation of patients and for their caregivers as it becomes difficult to sit affected patients in a wheel chair, make them eat or dress as the affected joints have lost their flexibility and are rigid. Furthermore, these heterotopic ossifications can entrap large blood vessels and nerves, increasing pain and paralysis. Heterotopic ossification following spine cord injuries was discovered 100 years ago on wounded Soldiers when the first X-ray radiography machines were deployed in France on the front line of World War I. Since then, there has been little progress in understanding why heterotopic ossifications develop in patients with spinal cord injuries and how to treat them to stop their growth in the body. Because of this lack of understanding, there is still no medicine to prevent or stop the formation and growth of these heterotopic ossifications in patients with spinal cord injuries. The only treatment is to remove these heterotopic ossifications by surgery when the ossifications have become very large and already further disabled the patients. These are complicated and long operations under general anesthesia as the patients are already fragilized by the spinal cord injury, and removing large ossifications around joints without damaging the joint, large blood vessels and nerves they entrap is very challenging with high risk of hemorrhage. Little progress has been made in the therapeutic treatment of heterotopic ossifications following spinal cord injuries because we still do not understand why and how they form in the first place. It is indeed not possible to take little samples of muscles from patients with spinal cord injuries to see and understand what happens because it is a very painful procedure that would damage the muscle. The only way forward to progress is to develop an animal model that replicates the complication in human patients. This is what we have done over the last 3 years. We have discovered that the spinal cord injury alone is not sufficient to cause the formation of heterotopic ossifications. It also needs a muscle inflammation. Most interestingly, a muscle inflammation alone is not sufficient to cause heterotopic ossification. In fact, it is only when the spinal cord injury is combined together with the muscle inflammation that heterotopic ossifications develop. This is in good agreement with what doctors observe as the patients with additional infections, wounds (particularly in battlefield wounded Soldiers), inflammation, bedsores are the most at risk of developing heterotopic ossification. We have also discovered that a special type of blood immune cells, which are recruited in inflamed wounds to repair it and fight infections, are responsible for these abnormal ossifications, and only if there is a spinal cord injury. We are now proposing to use our mouse model of heterotopic ossification caused by spinal cord injuries to understand the molecular mechanisms of why this happens and to test experimental and already used medicines to block this process. As we are the first ones to have been able to cause heterotopic ossifications in an ani
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510606
Entities
People
- Jean-Pierre Lévesque
Organizations
- United States Army
- University of Queensland