Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action.
Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action.
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DOI：
10.1016/j.jsbmb.2009.02.007
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Harvey EJ
中科院分区：
文献类型：
--
作者：
Kerachian MA;Séguin C;Harvey EJ
糖皮质激素（GC）的使用是股骨头坏死（ON）最常见的非创伤性原因。尽管GC与ON密切相关，但其潜在机制尚不清楚。研究人员提出了GC对细胞的直接和间接影响。间接和直接机制仍然密切相关，并经常导致积极的反馈循环，以加强疾病的进程。然而，直接的影响，特别是细胞凋亡，最近已被证明是越来越重要。成骨细胞和破骨细胞前体产生的抑制、成骨细胞和骨细胞凋亡的增加、破骨细胞寿命的延长和内皮细胞（EC）的凋亡都是GC使用的直接影响。通过几种途径升高血压可能会增加血栓形成的风险。高剂量GC还降低组织纤溶酶原激活物活性（t-PA）并增加血浆纤溶酶原激活物抑制物-1（派-1）抗原水平，从而增加GC的促凝血潜力。抑制血管生成，改变骨修复和一氧化氮代谢也可以导致。此外，GC治疗调节其他血管活性介质，如内皮素-1，去甲肾上腺素和缓激肽。因此，GC通过调节血管对血管活性物质的反应性来作为局部血流的调节剂。骨内股骨头动脉引起的血管收缩导致股骨头缺血。GC还通过增加骨内压引起缺血，其随后通过EC的凋亡以及提高骨髓中脂肪生成和脂肪肥大的水平来减少流向股骨头的血流量。很难预测哪些接受特定剂量GC的患者会发展为ON，这表明类固醇敏感性的个体差异和其他机制的潜力。ON的教科书模型是一种多重打击理论，其中，随着风险因素的增加，ON的风险增加。虽然需要更多的努力来更好地理解GC在ON中的作用，但关于GC对内皮细胞作用的最新数据和区域内皮床功能障碍理论为特定的GC机制提供了新的见解。更好地理解GC病理机制可以导致更好的治疗选择。
Glucocorticoid (GC) usage is the most common non-traumatic cause of osteonecrosis of the femoral head (ON). Despite the strong association of GC with ON, the underlying mechanisms have been unclear. Investigators have proposed both direct and indirect effects of GC on cells. Indirect and direct mechanisms remain intimately related and often result in positive feedback loops to potentiate the disease processes. However, the direct effects, in particular apoptosis, have recently been shown to be increasingly important. Suppression of osteoblast and osteoclast precursor production, increased apoptosis of osteoblasts and osteocytes, prolongation of the lifespan of osteoclasts and apoptosis of endothelial cells (EC) are all direct effects of GC usage. Elevated blood pressure through several pathways may raise the risk of clot formation. High-dose GC also decreases tissue plasminogen activator activity (t-PA) and increases plasma plasminogen activator inhibitor-1 (PAI-1) antigen levels increasing the procoagulant potential of GC. Inhibited angiogenesis, altered bone repair and nitric oxide metabolism can also result. Also, GC treatment modulates other vasoactive mediators such as endothelin-1, noradrenalin and bradykinin. Thus, GCs act as a regulator of local blood flow by modulating vascular responsiveness to vasoactive substances. Vasoconstriction induced in intraosseous femoral head arteries causes femoral head ischemia. GCs also cause ischemia through increased intraosseous pressure, which subsequently decreases the blood flow to the femoral head by apoptosis of ECs as well as elevating the level of adipogenesis and fat hypertrophy in the bone marrow. It is difficult to predict which patients receiving a specific dose of GC will develop ON, indicating individual differences in steroid sensitivity and the potential of additional mechanisms. The textbook model of ON is a multiple hit theory in which, with a greater number of risk factors, the risk of ON increases. While more effort is needed to better comprehend the role of GC in ON, newer data on GC action upon the endothelial cell and the regional endothelial bed dysfunction theory sheds new light on particular GC mechanisms. Better understanding of GC pathomechanisms can lead to better treatment options.
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影响因子：
4.5
作者：
Chan MH;Chan PK;Griffith JF;Chan IH;Lit LC;Wong CK;Antonio GE;Liu EY;Hui DS;Suen MW;Ahuja AT;Sung JJ;Lam CW
通讯作者：
Lam CW
DOI：
10.1302/0301-620x.86b8.14834
发表时间：
2004-11-01
影响因子：
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作者：
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通讯作者：
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DOI：
10.1097/01.blo.0000127587.92303.b4
发表时间：
2004-06-01
影响因子：
4.2
作者：
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通讯作者：
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DOI：
10.1016/0022-4731(90)90259-u
发表时间：
1990-03-01
影响因子：
4.1
作者：
CARBONE, JP;BALDRIDGE, RC;BRENT, RL
通讯作者：
BRENT, RL
影响因子：
4
作者：
Dempster, DW;Moonga, BS;Antakly, T
通讯作者：
Antakly, T