激素性股骨头坏死发生机制的新认识

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摘要糖皮质激素应用是股骨头坏死最常见的非创伤性原因，研究认为其发生机制包含直接和间接两重作用。直接作用包括：成骨细胞与破骨细胞前体生成抑制，成骨细胞与骨细胞凋亡，破骨细胞寿命延长，内皮细胞凋亡；间接作用包括：促进凝血活性，干扰血管再生，影响骨修复，调节局部血管收缩，诱导骨髓脂肪生成，增高髓内压。多种途径的激活使股骨头血供减少，从而导致坏死发生。此外，激素性股骨头坏死的发生还存在个体敏感性差异及其他的潜在机制，其患病模型为多重命中理论，风险因素越多则患病概率越大。应更深入地认识糖皮质激素的详细作用机制，从而为临床治疗提供更好的选择。

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	邓爽彭昊

关键词 ：糖皮质激素, 股骨头坏死, 成骨细胞, 破骨细胞, 骨细胞, 内皮细胞, 凋亡

Abstract：The use of glucocorticoids is the most common non-traumatic cause of osteonecrosis of the femoral head. Studies have shown that glucocorticoids can act directly or indirectly. Direct effects include inhibition of osteoblast and osteoclast precursor formation, apoptosis of osteoblasts and osteocytes, prolongation of osteoclast lifespan and apoptosis of endothelial cells. Indirect effects include increasing the risk of clot formation, inhibiting angiogenesis, interfering with bone repair, causing local vessel contraction, promoting lipogenesis in the bone marrow and increasing intramedullary pressure. Multiple pathway activation leads to the decrease of blood supply of the femoral head, resulting in osteonecrosis. Besides, there are individual differences in steroid sensitivity and other underlying mechanisms. The disease model is a multiple hit theory. The more risk factors, the greater probability of disease. More work is needed to better discover the pathomechanisms of glucocorticoids in osteonecrosis, so as to provide better choice for clinical treatment.

Key words： Glucocorticoid Osteonecrosis of the femoral head Osteoblast Osteoclast Osteocytes Endothelial cell Apoptosis

基金资助:国家自然科学基金资助项目（81672154）。

通讯作者: 彭昊（1963.7-），男，博士，主任医师，教授；研究方向：股骨头坏死与骨关节炎的基础与临床研究。

作者简介: 邓爽（1989.11-），女，武汉大学第一临床学院2015级骨外科学专业在读博士研究生；研究方向：股骨头坏死与骨关节炎的基础与临床研究。

引用本文:

邓爽彭昊. 激素性股骨头坏死发生机制的新认识[J]. 中国医药导报, 2017, 14(34): 29-32.
DENG Shuang PENG Hao. New understanding of pathogenesis of steroid induced osteonecrosis of the femoral head. 中国医药导报, 2017, 14(34): 29-32.

链接本文:

http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2017/V14/I34/29

[1] Assouline-Dayan Y，Chang C，Greenspan A，et al. Pathog?鄄enesis and natural history of osteonecrosis [J]. Semin Art?鄄hritis Rheum，2002，32（2）：94-124.
[2] Felson DT，Anderson JJ. Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone [J]. Lancet，1987，1（8538）：902-906.
[3] Zadegan F，Raould A，Bizot P，et al. Osteonecrosis after allogeneic bone marrow transplantation [J]. Clin Orthop Relat Res，2008，466（2）：287-293.
[4] Kerachian MA，Harvey EJ，Cournoyer D，et al. Avascular necrosis of the femoral head：vascular hypotheses [J]. Endothelium，2006，13（4）：237-244.
[5] Bejar J，Peled E，Boss JH，et al. Vasculature deprivation-induced osteonecrosis of the rat femoral head as a model for therapeutic trials [J]. Theor Biol Med Model，2005，2：24.
[6] Calder JD，Buttery L，Revell PA，et al. Apoptosis——a significant cause of bone cell death in osteonecrosis of the femoral head [J]. J Bone Joint Surg Br，2004，86（8）：1209-1213.
[7] Weinstein RS，Chen JR，Powers CC，et al. Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids [J]. J Clin Invest，2002，109（8）：1041-1048.
[8] Weinstein RS，Jilka RL，Parfitt AM，et al. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids，Potential mechanisms of their deleterious effects on bone [J]. J Clin Invest，1998， 102（2）：274-282.
[9] Zalavras C，Shah S，Birnbaum MJ，et al. Role of apoptosis in glucocorticoid-induced osteoporosis and osteonecrosis [J]. Crit Rev Eukaryot Gene Expr，2003，13（2-4）：221-235.
[10] Harper RN，Moore MA，Marr MC，et al. Arteriolar rarefaction in the conjunctiva of human essential hypertensives [J]. Microvasc Res，1978，16（3）：369-372.
[11] Boss JH，Misselevich I. Osteonecrosis of the femoral head of laboratory animals：the lessons learned from a comparative study of osteonecrosis in man and experimental animals [J]. Vet Pathol，2003，40（4）：345-354.
[12] He W，Xu C，FanY，et al. Effects of the Chinese drugs for activating blood circulation on plasma TXB2 and 6-keto-PGF1alpha contents in rabbits with glucocorticoid-induced femoral head necrosis [J]. J Tradit Chin Med，2004， 24（3）：233-237.
[13] Gray E，Thomas S，Mistry Y，et al. Inhibition of tissue factor and cytokine release [J]. Haemostasis，1996，26（Suppl 1）：92-95.
[14] Minneci PC，Deans KJ，Banks SM，et al. Meta-analysis：the effect of steroids on survival and shock during sepsis depends on the dose [J]. Ann Intern Med，2004，141（1）：47-56.
[15] Van Giezen JJ，Jansen JW. Correlation of in vitro and in vivo decreased fibrinolytic activity caused by dexamethasone [J]. Ann N Y Acad Sci，1992，667：199-201.
[16] Van Giezen JJ，Brakkee JG，Dreteler GH，et al. Dexamethasone affects platelet aggregation and fibrinolytic activity in rats at different doses which is reflected by their effect on arterial thrombosis [J]. Blood Coagul Fibrinolysis，1994，5（2）：249-255.
[17] Zangari M，Anaissie E，Barlogie B，et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy [J]. Blood，2001，98（5）：1614-1615.
[18] Smith DW. Is avascular necrosis of the femoral head the result of inhibition of angiogenesis？[J]. Med Hypotheses，1997，49（6）：497-500.
[19] Yamamoto Y，Ishizu A，Ikeda H，et al. Dexamethasone increased plasminogen activator inhibitor-1 expression on human umbilical vein endothelial cells：an additive effect to tumor necrosis factor-alpha [J]. Pathobiology，2004，71（6）：295-301.
[20] Yang C，Yang S，Du J，et al. Vascular endothelial growth factor gene transfection to enhance the repair of avascular necrosis of the femoral head of rabbit [J]. Chin Med J （Engl），2003，116（10）：1544-1548.
[21] Yang C，Yang S，Du J，et al. Experimental study of vascular endothelial growth factor gene therapy for avascular necrosis of the femoral head [J]. J Huazhong Univ Sci Technolog Med Sci，2003，23（3）：297-299，316.
[22] Li X，Jin L，Cui Q，et al. Steroid effects on osteogenesis through mesenchymal cell gene expression [J]. Osteoporos Int，2005，16（1）：101-108.
[23] Wada M，Kumagai K，Murata M，et al. Warfarin reduces the incidence of osteonecrosis of the femoral head in spontaneously hypertensive rats [J]. J Orthop Sci，2004，9（6）：585-590.
[24] Akaike M，Matsumoto T. Glucocorticoid-induced reduction in NO bioavailability and vascular endothelial dysfunction [J]. Clin Calcium，2007，17（6）：864-870.
[25] Drescher W，Li H，Lundgaard A，et al. Endothelin-1-induced femoral head epiphyseal artery constriction is enhanced by long-term corticosteroid treatment [J]. J Bone Joint Surg Am，2006，88（Suppl 3）：173-179.
[26] Drescher W，Varoga D，Liebs TR，et al. Femoral artery constriction by norepinephrine is enhanced by methylprednisolone in a rat model [J]. J Bone Joint Surg Am，2006， 88（Suppl 3）：162-166.
[27] Miyanishi K，Yamamoto T，Irisa T，et al. Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis [J]. Bone，2002， 30（1）：185-190.
[28] Zhou Q，Li Q，Yang L，et al. Changes of blood vessels in glucocorticoid-induced avascular necrosis of femoral head in rabbits [J]. Zhonghua Wai Ke Za Zhi，2000，38（3）：212-215.
[29] Yin L，Li YB，Wang YS. Dexamethasone-induced adipogenesis in primary marrow stromal cell cultures：mechanism of steroid-induced osteonecrosis [J]. Chin Med J （Engl），2006，119（7）：581-588.
[30] Jones JP，Ramirez S，Doty SB. The pathophysiologic role of fat in dysbaric osteonecrosis [J]. Clin Orthop Relat Res，1993（296）：256-264.
[31] Korompilias AV，Gilkeson GS，Seaber AV，et al. Hemorrhage and thrombus formation in early experimental osteonecrosis [J]. Clin Orthop Relat Res，2001（386）：11-18.
[32] Koch CA，Tsigos C，Patronas NJ，et al. Cushing's disease presenting with avascular necrosis of the hip：an orthopedic emergency [J]. J Clin Endocrinol Metab，1999，84（9）：3010-3012.
[33] Posan E，Harsfalvi J，Szepesi K，et al. Increased platelet activation and decreased fibrinolysis in the pathogenesis of aseptic necrosis of the femoral head [J]. Platelets，1998， 9（3-4）：233-235.
[34] Ferrari P，Schroeder V，Anderson S，et al. Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients [J]. Transplantation，2002，74（8）：1147-1152.
[35] Jones JP. Coagulopathies and osteonecrosis [J]. Acta Orthop Belg，1999，65（Suppl 1）：5-8.
[36] Jones LC，Mont MA，Le TB，et al. Procoagulants and osteonecrosis [J]. J Rheumatol，2003，30（4）：783-791.
[37] Asano T，Takahashi KA，FujiokM，et al. Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects [J]. Transplantation，2004，77（2）：220-225.
[38] Seguin C，Kassis J，Busque L，et al. Non-traumatic necrosis of bone（osteonecrosis）is associated with endothelial cell activation but not thrombophilia [J]. Rheumatology （Oxford），2008，47（8）：1151-1155.
[39] Khan A，Illiffe G，Houston DS，et al. Osteonecrosis in a patient with Crohn's disease unrelated to corticosteroid use [J]. Can J Gastroenterol，2001，15（11）：765-768.
[40] Freeman HJ，Kwan WC. Brief report：non-corticosteroid-associated osteonecrosis of the femoral heads in two patients with inflammatory bowel disease [J]. N Engl J Med，1993，329（18）：1314-1316.
[41] Koller E，Mann M，Malozowski S，et al. Aseptic necrosis in HIV seropositive patients：a possible etiologic role for megestrol acetate [J]. AIDS Patient Care STDS，2000，14（8）：405-410.
[42] Scribner AN，Troia-Cancio PV，Cox BA，et al. Osteonecrosis in HIV：a case-control study [J]. J Acquir Immune Defic Syndr，2000，25（1）：19-25.
[43] Schulte CM，Beelen DW. Vascular osteonecrosis after allogeneic hematopoietic stem-cell transplantation：diagnosis and gender matter [J]. Transplantation，2004，78（7）：1055-1063.