Pathogenesis of glucocorticoid-induced osteonecrosis of the femeral head

doi:10.3877/cma.j.issn.1673-9450.2015.05.016

Abstract

Abstract:

The pathophysiology of non-traumatic osteonecrosis of the femoral head is more complex than that of traumatic osteonecrosis, and corticosteroid-induced osteonecrosis presents a huge challenge because of the multiple effects of corticosteroids on multi-system pathways. These pathways include the effects of corticosteroids on osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, coagulation pathways, and calcium metabolism. These pathways are frequently interrelated with each other, which makes the pathogenesis even more difficult to understand. Host factors and underlying disease have been shown to play a significant role in the risk of developing osteonecrosis. Identification of genetic variants that convey additional risk will also help to personalize the way we care, both in the prevention and treatment of osteonecrosis.

Key words: Glucocorticoids, Femur head necrosis, Therapeutics, Pathogenesis

Liang Wang, Yaosheng Liu, Shubin Liu. Pathogenesis of glucocorticoid-induced osteonecrosis of the femeral head[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2015, 10(05): 439-445.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhssyxfzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1673-9450.2015.05.016

https://zhssyxfzz.cma-cmc.com.cn/EN/Y2015/V10/I05/439

References 70

1	Powell C, Chang C, Naguwa SM, et al. Steroid induced osteonecrosis: An analysis of steroid dosing risk[J]. Autoimmun Rev, 2010, 9(11): 721-743.
2	Jones LC, Mont MA, Le TB, et al. Procoagulants and osteonecrosis[J]. J Rheumatol, 2003, 30(4): 783-791.
3	Jones JP Jr. Coagulopathies and osteonecrosis[J]. Acta Orthop Belg, 1999, 65 Suppl 1: 5-8.
4	Chandler FA . Coronary disease of the hip[J]. J Int Coll Surg, 1948, 11(1): 34-36.
5	刘耀升，刘蜀彬. 早中期股骨头坏死的非手术治疗进展[J/CD]. 中华损伤与修复杂志：电子版，2012, 7(6): 668-670.
6	Hayashi S, Fujioka M, Ikoma K, et al. Evaluation of femoral perfusion in a rabbit model of steroid-induced osteonecrosis by dynamic contrast-enhanced mri with a high magnetic field MRI system[J]. J Magn Reson Imaging, 2015, 41(4): 935-940.
7	Janke LJ, Liu C, Vogel P, et al. Primary epiphyseal arteriopathy in a mouse model of steroid-induced osteonecrosis[J]. Am J Pathol, 2013, 183(1): 19-25.
8	Kerachian MA, Séguin C, Harvey EJ. Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action[J]. J Steroid Biochem Mol Biol, 2009, 114(3-5): 121-128.
9	Tian L, Zhou DS, Wang KZ, et al. Association of toll-like receptor 4 signaling pathway with steroid-induced femoral head osteonecrosis in rats[J]. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(5): 679-686.
10	Tian L, Wen Q, Dang X, et al. Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis[J]. BMC Musculoskelet Disord, 2014, 15: 18.
11	Weinstein RS, Nicholas RW, Manolagas SC. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip[J]. J Clin Endocrinol Metab, 2000, 85(8): 2907-2912.
12	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.
13	Wang L, Luo DK, Pan ZY. Expression of 11β-HSD in steroid-induced avascular necrosis of the femoral head[J]. Mol Med Rep, 2013, 7(5): 1482-1486.
14	Wu X, Yang S, Wang H, et al. G-CSF/SCF exert beneficial effects via anti-apoptosis in rabbits with steroid-associated osteonecrosis[J]. Exp Mol Pathol, 2013, 94(1): 247-254.
15	Tian L, Dang XQ, Wang CS, et al. Effects of sodium ferulate on preventing teroid-induced femoral head osteonecrosis in rabbits[J]. J Zhejiang Univ Sci B, 2013, 14(5): 426-437.
16	Moriishi T, Maruyama Z, Fukuyama R, et al. Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis[J]. PLoS One, 2011, 6(11): e27487.
17	Ookawa K, Tsuchida S, Adachi J, et al. Differentiation induced by RB expression and apoptosis induced by p53 expression in an osteosarcoma cell line[J]. Oncogene, 1997, 14(12): 1389-1396.
18	Kogianni G, Mann V, Ebetino F, et al. Fas/CD95 is associated with glucocorticoidinduced osteocyte apoptosis[J]. Life Sci, 2004, 75(24): 2879-2895.
19	Samara S, Dailiana Z, Chassanidis C, et al. Expression profile of osteoprotegerin RANK and RANKL genes in the femoral head of patients with avascular necrosis[J]. Exp Mol Pathol, 2014, 96(1): 9-14.
20	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.
21	Kerachian MA, Harvey EJ, Cournoyer D, et al. Avascular necrosis of the femoral head: vascular hypotheses[J]. Endothelium, 2006, 13(4): 237-244.
22	Feng Y, Yang SH, Xiao BJ, et al. Decreased in the numbe and function of circulation endothelial progenitor cells in patients with avascular necrosis of the femoral head[J]. Bone, 2010, 46(1): 32-40.
23	Li YM, Wang SX, Gao HS, et al. Factors of avascular necrosis of femoral head and osteoporosis in SARS patients' convalescence[J]. Zhonghua Yi Xue Za Zhi, 2004, 84(16): 1348-1353.
24	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.
25	Li C, Shen L, Yang Y, et al. Plasma ghrelin and von Willebrand Factor levels in patients with non-traumatic osteonecrosis of the femoral head[J]. Hip Int, 2015, 25(1): 76-81.
26	Kang P, Shen B, Yang J, et al. Circulating platelet-derived microparticles and endothelium-derived microparticles may be a potential cause of microthrombosis in patients with osteonecrosis of the femoral head[J]. Thromb Res, 2008, 123(2): 367-373.
27	Wu Z, Ji C, Li H, et al. Elevated level of membrane microparticles in the disease of steroid-induced vascular osteonecrosis[J]. J Craniofac Surg, 2013, 24(4): 1252-1256.
28	Chotanaphuti T, Heebthamai D, Chuwong M, et al. The prevalence of thrombophilia in idiopathic osteonecrosis of the hip[J]. J Med Assoc Thai, 2009, 92 Suppl 6: S141-S146.
29	Glueck CJ, Freiberg RA, Boppana S, et al. Thrombophilia, hypofibrinolysis, the eNOS T-786 C polymorphism, and multifocal osteonecrosis[J]. J Bone Joint Surg Am, 2008, 90(10): 2220-2229.
30	Glueck CJ, Freiberg RA, Wang P. Heritable thrombophilia-hypofibrinolysis and osteonecrosis of the femoral head[J]. Clin Orthop Relat Res, 2008, 466(5): 1034-1040.
31	Yamaguchi R1, Yamamoto T, Motomura G, et al. Effects of an anti-platelet drug on the prevention of steroid-induced osteonecrosis in rabbits[J]. Rheumatology (Oxford), 2012, 51(1): 789-793.
32	Arlet J, Ficat P, Lartigue G, et al. Clinical research on intraosseous pressure in the upper femoral metaphysis and epiphysis in humans. Application to the diagnosis of ischemia and necrosis[J]. Rev Rhum Mal Osteo-artic, 1972, 39(11): 717-723.
33	Cheng X, Hu B, Sheng J, et al. [Preliminary analysis of differentially expressed genes in steroid-induced osteonecrosis of femoral head by gene microarray][J]. Zhong guo Xiu Fu Chong Jian Wai Ke Za Zhi, 2014, 28(5): 586-590.
34	Wang KZ, Wang CS, Wu YG, et al. [Changes of vessel in steroid-induced osteonecrosis of femoral head: experimental study of rabbits][J]. Zhong hua Yi Xue Za Zhi, 2006, 86(29): 2024-2027.
35	Atsumi T, Kuroki Y. Role of impairment of blood supply of the femoral head in the pathogenesis of idiopathic osteonecrosis[J]. Clin Orthop Relat Res, 1992, 277: 22-30.
36	Welch RD, Johnston CE 2nd, Waldron MJ, et al. Bone changes associated with intraosseous hypertension in the caprine tibia[J]. J Bone Joint Surg Am, 1993, 75(1): 53-60.
37	Harada I. [The effects of glucocorticoids on angiogenesis in vitro][J]. Nihon Seikeigeka Gakkai Zasshi, 1992, 66(7): 763-770.
38	Li J, Fan L, Yu Z, et al. The effect of deferoxamine on angiogenesis and bone repair in steroid-induced osteonecrosis of rabbit femoral heads[J]. Exp Biol Med (Maywood), 2015, 240(2): 273-280.
39	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(297-299): 316.
40	Lee YJ, Lee JS, Kang EH, et al. Vascular endothelial growth factor polymorphisms in patients with steroid-induced femoral head osteonecrosis[J]. J Orthop Res, 2012, 30(1): 21-27.
41	Ikemura S, Yamamoto T, Motomura G, et al. Preventive effects of the anti-vasospasm agent via the regulation of the Rho-kinase pathway on the development of steroid-induced osteonecrosis in rabbits[J]. Bone, 2013, 53(2): 329-335.
42	Ichiseki T, Matsumoto T, Nishino M, et al. Oxidative stress and vascular permeability in steroidinduced osteonecrosis model[J]. J Orthop Sci, 2004, 9(5): 509-515.
43	Ichiseki T, Matsumoto T. Oxidative stress may underlie the sex differences seen in steroid-induced osteonecrosis models[J]. Med Hypotheses, 2006, 66(6): 1256.
44	Song Q, Shi Z, Bi W, et al. Beneficial effect of grape seed proanthocyanidin extract in rabbits with steroid-induced osteonecrosis via protecting against oxidative stress and apoptosis[J]. J Orthop Sci, 2015, 20(1): 196-204.
45	Li GY, Feng Y, Cheng TS, et al. Edaravone, a novel free radical scavenger, prevents steroid-induced osteonecrosis in rabbits[J]. Rheumatology (Oxford), 2013, 52(3): 438-447.
46	Kömürcü E, Oktay M, Kaymaz B, et al. Preventive effects of coenzyme Q10 (CoQ10) on steroid-induced osteonecrosis in rats[J]. Acta Orthop Traumatol Turc, 2014, 48(2): 217-222.
47	Jaffe WL, Epstein M, Heyman N, et al. The effect of cortisone on femoral and humeral heads in rabbits. An experimental study[J]. Clin Orthop Relat Res, 1972, 82: 221-228.
48	Chen XC, Weng J, Chen XQ, et al. Relationships among magnetic resonance imaging, histological findings, and IGF-I in steroid-induced osteonecrosis of the femoral head in rabbits[J]. J Zhejiang Univ Sci B, 2008, 9(9): 739-746.
49	Li W, Wang X, Liu B, et al. [Preventing steroid-induced osteonecrosis of the femoral head with Liuwei dihuang pills and molecular mechanism][J]. Zhong guo Xiu Fu Chong Jian Wai Ke Za Zhi, 2010, 24(4): 446-451.
50	Ding S, Peng H, Fang HS, et al. Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis in rats[J]. BMC Musculoskelet Disord, 2011, 12: 215.
51	Motomura G, Yamamoto T, Irisa T, et al. Dose effects of corticosteroids on the development of osteonecrosis in rabbits[J]. J Rheumatol, 2008, 35(12): 2395-2399.
52	Motomura G, Yamamoto T, Miyanishi K, et al. Risk factors for developing osteonecrosis after prophylaxis in steroid-treated rabbits[J]. J Rheumatol, 2008, 35(12): 2391-2394.
53	Kaneshiro Y, Oda Y, Iwakiri K, et al. Low hepatic cytochrome P450 3A activity is a risk for corticosteroid-induced osteonecrosis[J]. Clin Pharmacol Ther, 2006, 80(4): 396-402.
54	Masada T, Iwakiri K, Oda Y, et al. Increased hepatic cytochrome P4503A activity decreases the risk of developing steroid-induced osteonecrosis in a rabbit model[J]. J Orthop Res, 2008, 26(1): 91-95.
55	Tokuhara Y, Wakitani S, Oda Y, et al. Low levels of steroid-metabolizing hepatic enzyme (cytochrome P450 3A) activity may elevate responsiveness to steroids and may increase risk of steroid-induced osteonecrosis even with low glucocorticoid dose[J]. J Orthop Sci, 2009, 14(6): 794-800.
56	Wang Z, Zhang Y, Kong X, et al. Association of a polymorphism in PON-1 gene with steroid-induced osteonecrosis of femoral head in Chinese Han population[J]. Diagn Pathol, 2013, 8: 186.
57	Zhang Y, Wang R, Li S, et al. Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese population[J]. Diagn Pathol, 2013, 8: 169.
58	Zhang Y, Kong X, Wang R, et al. Genetic association of the P-glycoprotein gene ABCB1 polymorphisms with the risk for steroid-inducedosteonecrosis of the femoral head in Chinese population[J]. Mol Biol Rep, 2014, 41(5): 3135-3146.
59	Ma XL, Liu ZP, Ma JX, et al. Dynamic expression of Runx2, Osterix and AJ18 in the femoral head of steroid-induced osteonecrosis in rats[J]. Orthop Surg, 2010, 2(4): 278-284.
60	Tong P, Wu C, Jin H, et al. Gene expression profile of steroid-induced necrosis of femoral head of rats[J]. Calcif Tissue Int, 2011, 89(4): 271-284.
61	Asano T, Takahashi KA, Fujioka M, et al. ABCB1 C3435T and G2677T/A polymorphism decreased the risk for steroidinduced osteonecrosis of the femoral head after kidney transplantation[J]. Pharmacogenetics, 2003, 13(11): 675-682.
62	Han N, Yan Z, Guo CA, et al. Effects of p-glycoprotein on steroid-induced osteonecrosis of the femoral head[J]. Calcif Tissue Int, 2010, 87(3): 246-253.
63	Zheng L, Wang W, Ni J, et al. Plasma interleukin 33 level in patients with osteonecrosis of femoral head: an alarmin for osteonecrosis of the femoral head[J]. J Investig Med, 2014, 62(3): 635-637.
64	Cuadrado MJ, Lopez-Pedrera C. Antiphospholipid syndrome[J]. Clin Exp Med, 2003, 3(3): 129-139.
65	Bekler H, Uygur AM, Gökçe A, et al. [The effect of steroid use on the pathogenesis of avascular necrosis of the femoral head: an animal model][J]. Acta Orthop Traumatol Turc, 2007, 47(1): 58-63.
66	Matsui M, Saito S, Ohzono K, et al. Experimental steroid-induced osteonecrosis in adult rabbits with hypersensitivity vasculitis[J]. Clin Orthop Relat Res, 1992, (277): 61-72.
67	Aimaiti A, Wufuer M, Wang YH, et al. Can bisphenol A diglycidyl ether (BADGE) administration prevent steroid-induced femoral head osteonecrosis in the early stage[J]. Med Hypotheses, 2011, 77(2): 282-285.
68	Li J, Li Y, Wang Y, et al. Preventive effects of siRNA targeting PPARγ gene on steroid-induced osteonecrosis in rabbits[J]. Connect Tissue Res, 2014, 55(5-6): 322-330.
69	Jiang Y, Liu D, Kong X, et al. Huogu I formula prevents steroid-induced osteonecrosis in rats by down-regulating PPARgamma expression and activating wnt/LRP5/beta-catenin signaling[J]. J Tradit Chin Med, 2014, 34(3): 342-350.
70	Jiang Y, Zhang Y, Zhang H, et al. Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPAR γ expression and activating Wnt signaling pathway[J]. Exp Biol Med (Maywood), 2014, 239(3): 347-335.

[1]	Peijie Li, Yongjie Qiao, Haoqiang Zhang, Jiankang Zeng, Fei Tan, Jiahuan Li, Jing Wang, Shenghu Zhou. Progress in diagnosis and treatment of periprosthetic infection with negative bacterial culture [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2023, 17(06): 827-833.
[2]	Zhengwen Xu, Zhen Li, Zhenyang Hou, Changzheng Su, Biao Zhu. Platelet rich plasma combined with bone grafting for treatment of early non-traumatic osteonecrosis of femoral head [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2023, 17(06): 773-779.
[3]	Honglue Tan, Jinyang Yu, Xiaotao Shi, Xiao Wang, Yanhao Yuan. Diagnosis and treatment of complications after medial unicompartmental knee arthroplasty [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2023, 17(02): 267-275.
[4]	Xinyuan Yu, Xusheng Li, Haoqiang Zhang, Ziyao Li, Shenghu Zhou, Yongjie Qiao, Ping Zhen, Xiaoyang Song, Wenhua Zhang. Outcome assessment of uncemented total hip replacement in young patients [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2023, 17(01): 11-18.
[5]	Bing Wang, Lei Li, Guanjun Sun, Shanwu Li, Yongjie Ye. Progress in treatment of ankle osteoarthritis [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2023, 17(01): 111-118.
[6]	Rui Ma, Pei Yang, Run Tian, Chunsheng Wang, Kunzheng Wang. Effect of robot-assisted core decompression and bone grafting fornecrosis of femoral head [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2023, 17(01): 123-128.
[7]	Mengdie Chen, Yangyang Lin, Min Hou. Research progress in the treatment of idiopathic condylar resorption [J]. Chinese Journal of Stomatological Research(Electronic Edition), 2022, 16(06): 393-397.
[8]	Maodi Gong, Tao Li, Wei Chen, Shuxiong Xu. Management experiences of a patient with recurrent fever after percutaneous nephrolithotomy after long-term oral glucocorticoid [J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(03): 284-287.
[9]	Jiaming Huang, Hongxia Duan, Yupeng Lai, Daji Wang, Xingjiao Liu, Xin Shen, Meiying Wang. Progress of research on mesenchymal transformation of renal resident cells in the chronicity of lupus nephritis [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2022, 11(06): 347-352.
[10]	Kai Tang, Zhengfeng Liu, Jiawei Song, Xiuzhen Lu. Research progress of corneal and scleral dellen [J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2023, 13(04): 231-235.
[11]	Qixin Li, Wei Chen. Pay attention to the application of digital therapy in the field of eye health [J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2023, 13(03): 129-133.
[12]	Zhangqing Feng, Liping Jing, Junhong Li. Advances on the superior oblique myokymia [J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2023, 13(01): 30-34.
[13]	Wenjie Li, Hong Lu. Research progress of uveitis associated with juvenile idiopathic arthritis [J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2023, 13(01): 40-44.
[14]	Gang Jin, Yingzhen Li, Wei Shi, Bo Li. Research progress of Parkinson's disease in pathophysiology [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2023, 13(05): 315-319.
[15]	Min Wang, Yan Zhang, Yingxi Wang, Long Zhao, Shuyue Xia. The roles of exosomes in chronic obstructive pulmonary disease [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2023, 11(01): 45-51.

Please choose a citation manager

Content to export