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定量使个体易患骨坏死的人口统计学、临床和病理生理学特征，以及（2.）开发生物疗法来保护髋关节。 成功治疗骨坏死的关键在于识别高危人群，并根据临床和病理生理学特征量化其风险。 本研究的第一个假设是，骨坏死特殊风险患者是具有潜在遗传凝血缺陷的患者，这些患者随后会受到环境挑战（例如皮质类固醇给药）。 第二个假设是，股骨头塌陷之前的早期骨坏死将对治疗技术做出反应，这些治疗技术改变了股骨头修复过程的性质，从而增加了髋关节的保护。 这些假设是通过三个具体的目标。 具体目标1将量化骨坏死的发病率和患病率，在风险人群中使用廉价的有限筛选MRI方案。 将检查X线片，以评估早期诊断导致在塌陷前阶段识别髋关节的程度，在此阶段髋关节保留是可能的。 构成骨坏死诱发因素的临床特征将在风险组的个体中确定。 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倾向是否构成骨坏死的遗传易感性。 特定目的1和2的研究设计是一项前瞻性、纵向、设盲确定骨坏死发生率和定量确定对骨坏死发展的贡献、特定疾病状态、皮质类固醇剂量、给药方案和途径以及是否存在基础纤维蛋白溶解减退和血栓形成倾向的研究。 具体目标3将确定生物技术用于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的有效性，从而保留髋关节。具体目标1和2的健康相关性是能够在早期阶段识别风险个体，预计治疗将最有效。 特定目标3的健康相关性是最大限度地提高治疗效果，从而最大限度地保护髋关节。 如果这些目标得以实现，一种新的方法，即早期诊断和骨修复的生物增强，可以引入骨坏死的治疗。

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.