IDENTIFICATION & TREATMENT OF OSTEONECROSIS OF THE HIP

本研究的长期目标是：(1)在前瞻性研究中确定和量化使个体易患骨坏死的人口学、临床和病理生理特征，以及(2)开发保存髋关节的生物疗法。成功治疗骨坏死的关键在于确定高危人群，并根据临床和病理生理特征量化其风险。本研究的第一个假设是，骨坏死的特殊风险患者是那些具有潜在的遗传凝血缺陷的患者，他们受到随后的环境挑战（例如皮质类固醇的施用）。第二种假设是，股骨头塌陷之前的早期骨坏死会对改变股骨头修复过程的性质的治疗技术产生反应，从而增加髋关节的保存。这些假设是通过三个具体目标来实现的。特异性目标1将量化骨坏死的发病率和流行程度，在有风险的人群中使用廉价的有限筛查MRI方案。将检查x线片，以评估早期诊断结果在多大程度上识别髋关节在塌陷前阶段，髋关节保存是可能的。构成骨坏死易感因素的临床特征将在高危人群中确定。具体目标2将确定，在高危人群中，遗传性低纤溶和血栓形成是否构成骨坏死的遗传易感性。特异性目的1和2的研究设计是前瞻性、纵向、盲法测定骨坏死的发生率，定量测定骨坏死发展的贡献、特定疾病状态、皮质类固醇剂量、给药方案和途径，以及潜在的低纤溶和血栓形成的存在。特异性目的3将确定生物技术对髋关节保存的有效性。将进行前瞻性、随机、对照、盲法试验，以确定重组人骨形态发生蛋白2、脱钙骨基质和脉冲电磁场增强股骨头骨修复从而保护髋关节的疗效。具体目标1和2与健康的相关性在于能够在早期阶段识别有风险的个体，在早期阶段，治疗将是最有效的。特异性目的3的健康相关性是最大化治疗效果，从而最大化髋关节保护。如果要达到这些目标，就可以采用一种新的方法，即早期诊断和骨修复的生物增强，来治疗骨坏死。

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.