Heterotopic ossification (HO)occurs within one to three months of spinal cord injury (SCI), and severely limits rehabilitation. HO develops rapidly and is often not recognized until relatively late after trauma and during rehabilitation, when the process is difficult to reverse. Development of HO can be retarded by indomethacin and disodium etidronate. However, prophylactic treatment is often given in suboptimal doses and may not be well tolerated by the patient. After diagnosis of HO, full strength doses are instituted, however, are now less effective in preventing HO development since the process has developed to a more committed stage. The best solution is to establish the diagnosis very early, at a physiological pre-commitment stage, which is reversible by optimal doses of therapy. Therefore, the major purpose of this proposal will test the hypothesis that: 1) SCI patients predisposed to develop HO can be identified by measuring early physiological events involved in HO (detected within one week after SCI); and 2) a hypothetical volume of physiologic activities occurring in the pre-committed stage of ossification development can be detected by nuclear medicine SPECT scanning which will correlate with the actual volume of HO at three months. These hypothesis will be tested by the following specific aims: 1) determine the appropriate nuclear medicine imaging methodologies and imaging times after injury to allow early detection of HO, patients will be studied at one, four and 12 weeks after SCI by Thallium-201 and Tc-99m MDP. This will lead to the validation of an optimum single screening test protocol to accurately identify SCI patients who will progress to develop HO. 2) conduct anatomic imaging by MRI at the same time points to determine the location and volume of; and 3) to determine correlations between rehabilitation clinical data and nuclear medicine and MRI scans. Accuracy will be facilitated by an established three dimensional reference system that can be filled with different contrast agents and used during both the nuclear medicine SPECT scans and MRI scanning. This allows co- localization and precise volume assessment of early physiologic activity correlated to the volume of HO detected by MRI. The following benefits to rehabilitation of spinal cord injury patients are anticipated: 1) cost effective and optimal timing of nuclear imaging scans to detect HO development at an early reversible stage; 2) fundamental knowledge regarding the developmental process of HO at different times will be revealed by Tc-99m imaging, Thallium-201 imaging, and MRI imaging. This information will help clarify the pathophysiology underlying HO initiation and commitment to formation; 3) the rate and magnitude of HO formation will be precisely quantitated, and correlated with parameters of spinal cord injury, and rehabilitation; 4) the imaging protocols developed here can be used to rapidly determine the efficacy of future therapeutic trials or rehabilitation protocols to decrease physiological events leading to formation of HO within the first week after SCI. Future early drug therapy protocols can be monitored for efficacy using these early physiologic predictors of HO formation, when the process is in a reversible stage.
|Singh, Rajendra S; Craig, Michael C; Katholi, Charles R et al. (2003) The predictive value of creatine phosphokinase and alkaline phosphatase in identification of heterotopic ossification in patients after spinal cord injury. Arch Phys Med Rehabil 84:1584-8|