CORR Insights®: CORR® ORS Richard A. Brand Award: Disruption in Peroxisome Proliferator-Activated Receptor- γ (PPARG) Increases Osteonecrosis Risk Through Genetic Variance and Pharmacologic Modulation.
CORR Insights®: CORR® ORS Richard A. Brand Award: Disruption in Peroxisome Proliferator-Activated Receptor- γ (PPARG) Increases Osteonecrosis Risk Through Genetic Variance and Pharmacologic Modulation.
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CORR Insights®：CORR® ORS Richard A. 品牌奖：过氧化物酶体增殖物激活受体-γ (PPARG) 的破坏通过遗传变异和药理学调节增加骨坏死风险。
DOI：
10.1097/corr.0000000000000789
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发表时间：
2019
影响因子：
4.2
通讯作者：
Goodman,StuartB
中科院分区：
文献类型：
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作者：
Goodman,StuartB
股骨头坏死 (ONFH) 是一种进行性、潜在的衰弱性疾病，可导致股骨头塌陷和随后的退行性关节炎 [1,5,6]。这种疾病影响处于职业生涯黄金时期的个人，通常是 20 至 50 岁之间。 50%以上的患者ONFH常为双侧，也常为多灶性；它不仅可以发生在股骨头上，还可以发生在膝盖、肩部和距骨等部位。其病因是多因素的，但人们对其知之甚少。影响因素包括长期酗酒、使用皮质类固醇、高凝状态和创伤。红斑狼疮和类风湿性关节炎等炎症性疾病，以及高脂血症、戈谢氏病、吸烟和某些药物等代谢异常也可能与这种情况有关。然而，许多患者的 ONFH 是特发性的，并且在没有任何明确病因的情况下发生。如果不进行干预，ONFH 通常会进展为股骨头塌陷、退行性关节炎，许多患者最终需要进行全髋关节置换术 [1,5,6]。减轻危险因素以及在股骨头塌陷之前进行早期诊断和治疗可能使我们能够保留患者的原生髋关节。这对于年轻和活跃的患者尤其重要。核心减压并添加从髂嵴采集的浓缩细胞可改善早期 ONFH 患者的预后 [1-3, 5]。然而，识别早期疾病患者很困难，因为患者通常直到疾病晚期才出现症状。现在有证据表明，一些骨坏死患者在凝血级联或参与细胞代谢、组织形成和修复的一个或多个生物途径中存在遗传异常[4, 7]。在当前的研究中，Wyles 和同事获得了 CORR® ORS RAB 骨科研究奖[7]，进一步阐明了为什么一些暴露于不同 ONFH 危险因素的患者会患上这种疾病，而其他人则可能不会。如上所述，以前曾怀疑代谢异常可能使某些患者容易发生骨坏死。 Wyles 及其同事 [7] 确定过氧化物酶体增殖物激活受体-g (PPARG) 的基因突变与 ONFH 的发生具有重要关系，PPARG 是脂肪酸储存和葡萄糖代谢的关键因素。
Osteonecrosis of the femoral head (ONFH) is a progressive, potentially debilitating disorder that leads to femoral head collapse and subsequent degenerative arthritis [1, 5, 6]. This disease affects individuals in the prime of their working lives, usually between 20 and 50 years of age. Bilateral in more than 50% of patients, ONFH often also is multifocal; it can occur not just in the femoral head, but also in the knee, the shoulder, and the talus, among other locations. Its etiology is multifactorial and poorly understood; contributing factors include chronic alcohol abuse, corticosteroid use, hypercoagulable states, and trauma. Inflammatory diseases such as lupus erythematosus and rheumatoid arthritis may also be associated with this condition, as are metabolic abnormalities like hyperlipidemia, Gaucher’s disease, smoking, and certain medications. However, ONFH in many patients is idiopathic, and occurs without any clear etiologic factors. Without intervention, ONFH generally progresses to femoral head collapse, degenerative arthritis and ultimately in many patients, total hip arthroplasty [1, 5, 6]. Mitigation of risk factors, and early diagnosis and treatment prior to femoral head collapse may allow us to retain a patient’s native hip joint. This is especially important in younger and more-active patients. Core decompression, with addition of concentrated cells harvested from the iliac crest improves the outcome for patients with early stage ONFH [1-3, 5]. However, identifying patients with early stage disease is difficult, because patients often do not become symptomatic until the disease is more advanced. There is now evidence that some patients with osteonecrosis have a genetic abnormality in the coagulation cascade, or in one or more biological pathways involved in cell metabolism, tissue formation and repair [4, 7].In the current study, which won the CORR® ORS RAB Award for Orthopaedic Research, Wyles and colleagues [7] shed further light as to why some patients exposed to different risk factors for ONFH develop this condition, and why others may not. As outlined above, it has been previously suspected that metabolic abnormalities may predispose some patients to osteonecrosis. Wyles and colleagues [7] have determined that genetic mutations in Peroxisome Proliferator-Activated Receptor-g (PPARG), a key factor in fatty acid storage and glucose metabolism, has an important relationship with the development of ONFH.