Pathogenesis of Heterotopic Ossification in Traumatic Brain Injury
JAMES A HALEY VA HOSPITAL TAMPA FL
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Heterotopic ossification HO is the pathologic formation of bone in soft tissues. HO develops during the physical rehabilitation of patients with traumatic injuries, such as brain, spinal cord or orthopedic injury. When adjacent to joints or pressure points, HO causes pain, pressure sores and physical obstruction that significantly limits rehabilitation. The incidence is as high as 50 after traumatic amputation due to blast injury, when the amputation is through damaged soft tissue. Much of the clinical management of HO has been empiric. We show that an atraumatic mouse model of subcutaneous HO reproduces essential features of clinical HO in humans. 1 There is an early inflammatory phase, 2 HO progresses towards bone maturity and 3 damaged soft tissue promotes local HO development. Preliminary attempts to activate osteoclast resorptive function in vivo failed, probably due to insufficient bioavailability and the rapid decline of osteoclast numbers after 2 weeks. Our observations show that this mouse model of HO an accessible and clinically relevant system for detailed in vivo analysis of HO pathogenesis and treatment. The mechanism of wound-exacerbated HO progression in mice may usefully inform the medical care of HO in amputated limbs. In the next 6 months we propose to confirm that COX2 inhibitors prevent HO progression in this model and to determine if FDA-approved vascular endothelial growth factor antagonists will disrupt endothelial formation and COX2 expression that are necessary for new bone formation in this mouse model.
- Anatomy and Physiology
- Medicine and Medical Research
- Stress Physiology