Prevention and Treatment of Heterotopic Ossification

Abstract : The factors contributing to heterotopic ossification (HO), the formation of bone in abnormal soft-tissue locations, are beginning to emerge, but very little is known about the microenvironmental conditions that promote this often devastating disease. Using a murine model in which endochondral bone formation is triggered in muscle by bone morphogenetic protein 2 (BMP2), we studied the changes near the site of injection of BMP2-expressing cells. We propose to study in more detail the role of adipocytes in heterotopic bone formation in order to prevent or treat heterotopic ossification. We will augment our current microarray analysis and immunohistochemical analysis of the kinetics of HO. We will compare, using histology, immunohistochemistry, and micro CT the mouse and human lesions. We will also address the reason that combat wounds are more likely than civilian trauma to develop heterotopic ossification. We hypothesize that there is a basic difference in the injury pattern/mechanism that may impact nerves, recapitulating spinal cord injury in which HO is a major problem. We therefore also plan to study the neuronal component of HO. Finally, it is important that in blocking HO we do not also block the normal fracture repair process; this latter process should be intact or even augmented.