The long-term objectives of this study are to (1.) determine and quantitate in prospective studies the demographic, clinical and pathophysiologic characteristics which predispose individuals to osteonecrosis, and (2.) develop biological therapies for hip preservation. The keys to the successful treatment of osteonecrosis lie in identifying at-risk populations and quantitating their risk in terms of clinical and pathophysiological characteristics. The first hypothesis of this study is that patients at special risk for osteonecrosis are those with an underlying genetic coagulation defect who are subject to subsequent environmental challenge (e.g. corticosteroid administration). The second hypothesis is that early stage osteonecrosis, before collapse of the femoral head, will respond to therapeutic techniques which alter the nature of the repair process in the femoral head resulting in increased hip preservation. These hypotheses are approached through three specific aims.
Specific Aim 1 will quantitate the incidence and prevalence of osteonecrosis, in at-risk populations with an inexpensive limited screening MRI protocol. Radiographs will be examined to assess the extent to which early diagnosis results in the identification of hips at a precollapse stage at which hip preservation is possible. Clinical features which constitute predisposing factors for osteonecrosis will be identified in individuals in at-risk groups.
Specific Aim 2 will determine, in the populations of at-risk individuals, whether or not inherited hypofibrinolysis and thrombophilia constitute a genetic predisposition to osteonecrosis. The research design for Specific Aims 1 and 2 is a prospective, longitudinal, blinded determination of the incidence of osteonecrosis and the quantitation of the contribution to the development of osteonecrosis, of the specific disease state, corticosteroid dose, regimen and route of administration, and the presence of underlying hypofibrinolysis and thrombophilia.
Specific Aim 3 will determine the efficacy of biological techniques for hip preservation. Prospective, randomized, controlled, blinded trials will be carried out to determine the efficacy of recombinant human bone morphogenic protein 2, decalcified bone matrix, and pulsed electromagnetic fields for the augmentation of bone repair in the femoral head resulting in hip preservation. The health relevance of Specific Aims 1 and 2 is the ability to identify at-risk individuals at an early stage, where treatment would be expected to be most effective. The health relevance of Specific Aim 3 is to maximize treatment efficacy and therefore maximize hip preservation. If these aims were to be achieved, a new approach, i.e. early diagnosis and biological augmentation of bone repair, could be introduced for the treatment of osteonecrosis.
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