Glucocorticoids in osteonecrosis of the femoral head: A new understanding of the mechanisms of action

Journal of Steroid Biochemistry and Molecular Biology

Volumn 114, Issue 3-5, 2009, Pages 121-128

  Kerachian, Mohammad Amin ^a   Séguin, Chantal ^b   Harvey, Edward J ^c  

^a MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^b MCGILL UNIVERSITY   (Canada)

^c MONTREAL GENERAL HOSPITAL   (Canada)

Author keywords

Avascular necrosis; Endothelial cells; Glucocorticoids; Osteonecrosis; Steroids

Indexed keywords

GLUCOCORTICOID; METHYLPREDNISOLONE; PLASMINOGEN ACTIVATOR INHIBITOR 1; TISSUE PLASMINOGEN ACTIVATOR;

ADIPOGENESIS; ANGIOGENESIS; APOPTOSIS; AVASCULAR NECROSIS; BLOOD CLOTTING; BLOOD FLOW; BONE REMODELING; CELL PROLIFERATION; ENDOTHELIUM CELL; FEMUR HEAD NECROSIS; HUMAN; LIPID METABOLISM; NONHUMAN; OSTEOBLAST; OSTEOCYTE; REVIEW; RISK FACTOR; VASOCONSTRICTION;

APOPTOSIS; BONE AND BONES; ENDOTHELIUM, VASCULAR; FEMUR HEAD; GLUCOCORTICOIDS; HUMANS; NEOVASCULARIZATION, PHYSIOLOGIC; OSTEONECROSIS;

EID: 63249102275     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2009.02.007     Document Type: Review

References (101)

1. Weinstein R.S., and Manolagas S.C. Apoptosis in glucocorticoid-induced bone disease. Curr. Opin. Endocrinol. Diabetes 12 (2008) 219-223
2. Koo K.H., Kim R., Kim Y.S., Ahn I.O., Cho S.H., Song H.R., et al. Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin. Rheumatol. 21 4 (2002) 299-303
3. Assouline-Dayan Y., Chang C., Greenspan A., Shoenfeld Y., and Gershwin M.E. Pathogenesis and natural history of osteonecrosis. Semin. Arthritis. Rheum. 32 2 (2002) 94-124
4. Felson D.T., and Anderson J.J. Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone. Lancet 1 8538 (1987) 902-906
5. Lafforgue P. Pathophysiology and natural history of avascular necrosis of bone. Joint Bone Spine 73 5 (2006) 500-507
6. Khan A., Illiffe G., Houston D.S., and Bernstein C.N. Osteonecrosis in a patient with Crohn's disease unrelated to corticosteroid use. Can. J. Gastroenterol. 15 11 (2001) 765-768
7. Liu Y.F., Chen W.M., Lin Y.F., Yang R.C., Lin M.W., Li L.H., et al. Type II collagen gene variants and inherited osteonecrosis of the femoral head. N. Engl. J. Med. 352 22 (2005) 2294-2301
8. Chen W.M., Liu Y.F., Lin M.W., Chen I.C., Lin P.Y., Lin G.L., et al. Autosomal dominant avascular necrosis of femoral head in two Taiwanese pedigrees and linkage to chromosome 12q13. Am. J. Hum. Genet. 75 2 (2004) 310-317
9. Posan E., Harsfalvi J., Szepesi K., Gaspar L., Batar P., and Udvardy M. Increased platelet activation and decreased fibrinolysis in the pathogenesis of aseptic necrosis of the femoral head. Platelets 9 3-4 (1998) 233-235
10. Glueck C.J., Fontaine R.N., Gruppo R., Stroop D., Sieve-Smith L., Tracy T., et al. The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis. Clin. Orthop. Relat. Res. 366 (1999) 133-146
11. Glueck C.J., Freiberg R.A., Fontaine R.N., Tracy T., and Wang P. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin. Orthop. 386 (2001) 19-33
12. Murata M., Kumagai K., Miyata N., Osaki M., and Shindo H. Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid. J. Orthop. Sci. 12 3 (2007) 289-295
13. Zadegan F., Raould A., Bizot P., Nizard R., and Sedel L. Osteonecrosis after allogeneic bone marrow transplantation. Clin. Orthop. Relat. Res. 466 2 (2008) 287-293
14. Kerachian M.A., Harvey E.J., Cournoyer D., Chow T.Y., and Seguin C. Avascular necrosis of the femoral head: vascular hypotheses. Endothelium 13 4 (2006) 237-244
15. Chen W.L., Lin C.T., Yao C.C., Huang Y.H., Chou Y.B., Yin H.S., et al. In-vitro effects of dexamethasone on cellular proliferation, apoptosis, and Na+-K+-ATPase activity of bovine corneal endothelial cells. Ocul. Immunol. Inflamm. 14 4 (2006) 215-223
16. Moraes L.A., Paul-Clark M.J., Rickman A., Flower R.J., Goulding N.J., and Perretti M. Ligand-specific glucocorticoid receptor activation in human platelets. Blood 106 13 (2005) 4167-4175
17. Dempster D.W., Moonga B.S., Stein L.S., Horbert W.L., and Antakly T. Glucocorticoids inhibit bone resorption by isolated rat osteoclasts by enhancing apoptosis. J. Endocrinol. 154 3 (1997) 397-406
18. Liesegang P., Romalo G., Sudmann M., Wolf L., and Schweikert H.U. Human osteoblast-like cells contain specific, saturable, high affinity glucocorticoid, androgen, estrogen, and 1 alpha, 25-dihydroxycholecalciferol receptors. J. Androl. 15 3 (1994) 194-199
19. Gu G., Hentunen T.A., Nars M., Härkönen P.L., and Väänänen H.K. Estrogenprotects primary osteocytes against glucocorticoid-induced apoptosis. Apoptosis 10 3 (2005) 583-595
20. Chen T.L., Aronow L., and Feldman D. Glucocorticoid receptors and inhibition of bone cell growth in primary culture. Endocrinology 100 3 (1977) 619-628
21. Conaway H.H., Grigorie D., and Lerner U.H. Stimulation of neonatal mouse calvarial bone resorption by the glucocorticoids hydrocortisone and dexamethasone. J. Bone Miner. Res. 11 10 (1996) 1419-1429
22. Yoshioka T., Sato B., Matsumoto K., and Ono K. Steroid receptors in osteoblasts. Clin. Orthop. Relat. Res. 148 (1980) 297-303
23. Silvestrini G., Mocetti P., Ballanti P., DiGrezia R., and Bonucci E. Cytochemical demonstration of the glucocorticoid receptor in skeletal cells of the rat. Endocrinol. Res. 25 1 (1999) 117-128
24. Kogianni G., Mann V., Ebetino F., Nuttall M., Nijweide P., Simpson H., et al. Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis. Life Sci. 75 24 (2004) 2879-2895
25. Khan A.A., Soloski M.J., Sharp A.H., Schilling G., Sabatini D.M., Li S.H., et al. Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor. Science 273 5274 (1996) 503-507
26. Wolff J.E., Guerin C., Laterra J., Bressler J., Indurti R.R., Brem H., et al. Dexamethasone reduces vascular density and plasminogen activator activity in 9L rat brain tumors. Brain Res. 604 1-2 (1993) 79-85
27. Bejar J., Peled E., and Boss J.H. Vasculature deprivation-induced osteonecrosis of the rat femoral head as a model for therapeutic trials. Theor. Biol. Med. Model. 2 (2005) 24
28. Weinstein R.S., Nicholas R.W., and Manolagas S.C. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J. Clin. Endocrinol. Metab. 85 8 (2000) 2907-2912
29. Calder J.D., Buttery L., Revell P.A., Pearse M., and Polak J.M. Apoptosis-a significant cause of bone cell death in osteonecrosis of the femoral head. J. Bone Joint Surg. Br. 86 8 (2004) 1209-1213
30. O'Brien C.A., Jia D., Plotkin L.I., Bellido T., Powers C.C., Stewart S.A., et al. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145 4 (2004) 1835-1841
31. Weinstein R.S., Chen J.R., Powers C.C., Stewart S.A., Landes R.D., Bellido T., et al. Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids. J. Clin. Invest. 109 8 (2002) 1041-1048
32. Weinstein R.S., Jilka R.L., Parfitt A.M., and Manolagas S.C. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J. Clin. Invest. 102 2 (1998) 274-282
33. Zalavras C., Shah S., Birnbaum M.J., and Frenkel B. Role of apoptosis in glucocorticoid-induced osteoporosis and osteonecrosis. Crit. Rev. Eukaryot. Gene Expr. 13 2-4 (2003) 221-235
34. Chang J.K., Ho M.L., Yeh C.H., Chen C.H., and Wang G.J. Osteogenic gene expression decreases in stromal cells of patients with osteonecrosis. Clin. Orthop. Relat. Res. 453 (2006) 286-292
35. Whitworth J.A., Brown M.A., Kelly J.J., and Williamson P.M. Mechanisms of cortisol-induced hypertension in humans. Steroids 60 1 (1995) 76-80
36. Harper R.N., Moore M.A., Marr M.C., Watts L.E., and Hutchins P.M. Arteriolar rarefaction in the conjunctiva of human essential hypertensives. Microvasc. Res. 16 3 (1978) 369-372
37. Boss J.H., and Misselevich I. Osteonecrosis of the femoral head of laboratory animals: the lessons learned from a comparative study of osteonecrosis in man and experimental animals. Vet. Pathol. 40 4 (2003) 345-354
38. Jacobs B. Epidemiology of traumatic and nontraumatic osteonecrosis. Clin. Orthop. Relat. Res. 130 (1978) 51-67
39. Li Y., Chen J., Zhang Z., Wang K., Tong Z., and Yan H. The experimental study on treatment of glucocorticoid-induced ischemic necrosis of femoral head by gu fu sheng capsule. J. Tradit. Chin. Med. 24 4 (2004) 303-307
40. He W., Xu C., Fan Y., Fang B., Li X., Wang H., 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. Tradit. Chin. Med. 24 3 (2004) 233-237
41. Vogt C.J., and Schmid-Schonbein G.W. Microvascular endothelial cell death and rarefaction in the glucocorticoid-induced hypertensive rat. Microcirculation 8 2 (2001) 129-139
42. Rajashree S., and Puvanakrishnan R. Dexamethasone induced alterations in the levels of proteases involved in blood pressure homeostasis and blood coagulation in rats. Mol. Cell Biochem. 197 1-2 (1999) 203-208
43. Gray E., Thomas S., Mistry Y., and Poole S. Inhibition of tissue factor and cytokine release. Haemostasis 26 Suppl (1996) 192-195
44. Minneci P.C., Deans K.J., Banks S.M., Eichacker P.Q., and Natanson C. Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann. Intern. Med. 141 1 (2004) 47-56
45. van Giezen J.J., and Jansen J.W. Correlation of in vitro and in vivo decreased fibrinolytic activity caused by dexamethasone. Ann. N.Y. Acad. Sci. 667 (1992) 199-201
46. van Giezen J.J., Brakkee J.G., Dreteler G.H., Bouma B.N., and Jansen J.W. Dexamethasone affects platelet aggregation and fibrinolytic activity in rats at different doses which is reflected by their effect on arterial thrombosis. Blood Coagul. Fibrinolysis 5 2 (1994) 249-255
47. Zangari M., Anaissie E., Barlogie B., Badros A., Desikan R., Gopal A.V., et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 98 5 (2001) 1614-1615
48. Smith D.W. Is avascular necrosis of the femoral head the result of inhibition of angiogenesis?. Med. Hypotheses 49 6 (1997) 497-500
49. Yamamoto Y., Ishizu A., Ikeda H., Otsuka N., and Yoshiki T. Dexamethasone increased plasminogen activator inhibitor-1 expression on human umbilical vein endothelial cells: an additive effect to tumor necrosis factor-alpha. Pathobiology 71 6 (2004) 295-301
50. Drescher W., Weigert K.P., Bunger M.H., Ingerslev J., Bunger C., and Hansen E.S. Femoral head blood flow reduction and hypercoagulability under 24 h megadose steroid treatment in pigs. J. Orthop. Res. 22 3 (2004) 501-508
51. Madsen P.V., and Andersen G. Multifocal osteonecrosis related to steroid treatment in a patient with ulcerative colitis. Gut 35 1 (1994) 132-134
52. Solarino G., Scialpi L., Bruno M., and De Cillis B. On a case of multifocal osteonecrosis in a patient suffering from acute lymphoblastic leukemia. Chir. Organi. Mov. 92 2 (2008) 119-122
53. Ferrari P., Schroeder V., Anderson S., Kocovic L., Vogt B., Schiesser D., et al. Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients. Transplantation 74 8 (2002) 1147-1152
54. Jones Jr. J.P. Coagulopathies and osteonecrosis. Acta. Orthop. Belg. 65 Suppl. 1 (1999) 5-8
55. Jones L.C., Mont M.A., Le T.B., Petri M., Hungerford D.S., Wang P., et al. Procoagulants and osteonecrosis. J. Rheumatol. 30 4 (2003) 783
56. Asano T., Takahashi K.A., Fujioka M., Inoue S., Ueshima K., Hirata T., et al. Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects. Transplantation 77 2 (2004) 220-225
57. Seguin C., Kassis J., Busque L., Bestawros A., Theodoropoulos J., Alonso M.L., et al. Non-traumatic necrosis of bone (osteonecrosis) is associated with endothelial cell activation but not thrombophilia. Rheumatology (Oxford) 47 8 (2008) 1151-1155
58. Slichter S.J., Stegall P., Smith K., Huang T.W., and Harker L.A. Dysbaric osteonecrosis: a consequence of intravascular bubble formation, endothelial damage, and platelet thrombosis. J. Lab Clin. Med. 98 4 (1981) 568-590
59. Aaron R.K., and Ciombor D.M. Coagulopathies and Osteonecrosis. Curr. Opin. Orthop. 12 (2001) 378-383
60. Dimmeler S., Haendeler J., and Zeiher A.M. Regulation of endothelial cell apoptosis in atherothrombosis. Curr. Opin. Lipidol. 13 5 (2002) 531-536
61. Yang C., Yang S., Du J., Li J., Xu W., and Xiong Y. Vascular endothelial growth factor gene transfection to enhance the repair of avascular necrosis of the femoral head of rabbit. Chin. Med. J. (Engl.) 116 10 (2003) 1544-1548
62. Yang C., Yang S., Du J., Li J., Xu W., and Xiong Y. Experimental study of vascular endothelial growth factor gene therapy for avascular necrosis of the femoral head. J. Huazhong Univ. Sci. Technolog Med. Sci. 23 3 (2003) 297-299 316
63. Li X., Jin L., Cui Q., Wang G.J., and Balian G. Steroid effects on osteogenesis through mesenchymal cell gene expression. Osteoporos. Int. 16 1 (2005) 101-108
64. Boss J.H. Experimental models of osteonecrosis of the femoral head. J. Orthop. Sci. 9 5 (2004) 533-534
65. Harada I. The effects of glucocorticoids on angiogenesis in vitro. Nippon Seikeigeka Gakkai Zasshi 66 7 (1992) 763-770
66. Glueck C.J., Freiberg R., Glueck H.I., Henderson C., Welch M., Tracy T., et al. Hypofibrinolysis: a common, major cause of osteonecrosis. Am. J. Hematol. 45 2 (1994) 156-166
67. Iuchi T., Akaike M., Mitsui T., Ohshima Y., Shintani Y., Azuma H., et al. Glucocorticoid excess induces superoxide production in vascular endothelial cells and elicits vascular endothelial dysfunction. Circ. Res. 92 1 (2003) 81-87
68. Wada M., Kumagai K., Murata M., Yamashita Y., and Shindo H. Warfarin reduces the incidence of osteonecrosis of the femoral head in spontaneously hypertensive rats. J. Orthop. Sci. 9 6 (2004) 585-590
69. Akaike M., and Matsumoto T. Glucocorticoid-induced reduction in NO bioavailability and vascular endothelial dysfunction. Clin. Calcium 17 6 (2007) 864-870
70. Drescher W., Li H., Lundgaard A., Bunger C., and Hansen E.S. Endothelin-1-induced femoral head epiphyseal artery constriction is enhanced by long-term corticosteroid treatment. J. Bone Joint Surg. Am. 88 Suppl. 3 (2006) 173-179
71. Drescher W., Bunger M.H., Weigert K., Bunger C., and Hansen E.S. Methylprednisolone enhances contraction of porcine femoral head epiphyseal arteries. Clin. Orthop. Relat. Res. 423 (2004) 112-117
72. Drescher W., Varoga D., Liebs T.R., Lohse J., Herdegen T., Hassenpflug J., et al. Femoral artery constriction by norepinephrine is enhanced by methylprednisolone in a rat model. J. Bone Joint Surg. Am. 88 Suppl. 3 (2006) 162-166
73. Rajashree S., and Puvanakrishnan R. Dexamethasone induced alterations in enzymatic and nonenzymatic antioxidant status in heart and kidney of rats. Mol. Cell Biochem. 181 1-2 (1998) 77-85
74. Miyanishi K., Yamamoto T., Irisa T., Yamashita A., Jingushi S., Noguchi Y., et al. Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis. Bone 30 1 (2002) 185-190
75. Zhou Q., Li Q., Yang L., and Liu F. Changes of blood vessels in glucocorticoid-induced avascular necrosis of femoral head in rabbits. Zhonghua Wai Ke Za Zhi 38 3 (2000) 212-215 13
76. Cui Q., Wang G.J., and Balian G. Steroid-induced adipogenesis in a pluripotential cell line from bone marrow. J. Bone Joint Surg. Am. 79 7 (1997) 1054-1063
77. Cui Q., Wang G.J., and Balian G. Pluripotential marrow cells produce adipocytes when transplanted into steroid-treated mice. Connect Tissue Res. 41 1 (2000) 45-56
78. Yin L., Li Y.B., and Wang Y.S. Dexamethasone-induced adipogenesis in primary marrow stromal cell cultures: mechanism of steroid-induced osteonecrosis. Chin. Med. J. (Engl.) 119 7 (2006) 581-588
79. Kitajima M., Shigematsu M., Ogawa K., Sugihara H., and Hotokebuchi T. Effects of glucocorticoid on adipocyte size in human bone marrow. Med. Mol. Morphol. 40 3 (2007) 150-156
80. Jones Jr. J.P., Ramirez S., and Doty S.B. The pathophysiologic role of fat in dysbaric osteonecrosis. Clin. Orthop. Relat. Res. 296 (1993) 256-264
81. Vadasz Z., Misselevich I., Norman D., Peled E., and Boss J.H. Localization of vascular endothelial growth factor during the early reparative phase of the rats' vessels deprivation-induced osteonecrosis of the femoral heads. Exp. Mol. Pathol. 77 2 (2004) 145-148
82. Rosenberg R.D., and Aird W.C. Vascular-bed-specific hemostasis and hypercoagulable states. N. Engl. J. Med. 340 20 (1999) 1555-1564
83. Korompilias A.V., Gilkeson G.S., Seaber A.V., and Urbaniak J.R. Hemorrhage and thrombus formation in early experimental osteonecrosis. Clin. Orthop. Relat. Res. 386 (2001) 11-18
84. Koch C.A., Tsigos C., Patronas N.J., and Papanicolaou D.A. Cushing's disease presenting with avascular necrosis of the hip: an orthopedic emergency. J. Clin. Endocrinol. Metab. 84 9 (1999) 3010-3012
85. Carbone J.P., Baldridge R.C., Koszalka T.R., Bongiovanni A.M., and Brent R.L. Characterization of cytosolic glucocorticoid receptor of fatal rat epiphyseal chondrocytes. J. Steroid Biochem. 35 3-4 (1990) 495-505
86. Cowell A.M., and Buckingham J.C. Glucocorticoid and the HPA axis. In: Nicolas J.G., and Flower R.J. (Eds). Glucocorticoids (2001), Birkhäuser, Switzerland 131
87. Chan M.H., Chan P.K., Griffith J.F., Chan I.H., Lit L.C., Wong C.K., et al. Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy. Pathology 38 3 (2006) 229-235
88. Hendry W.F. Bilateral aseptic necrosis of femoral heads following intermittent high-dose steroid therapy. Fertil. Steril. 38 1 (1982) 120
89. Skinner J.A., Mann B.S., Carrington R.W., Hashems-Nejad A., and Bentley G. Male infertility and avascular necrosis of the femoral head. Ann. R. Coll. Surg. Engl. 86 1 (2004) 15-17
90. Mistlin A., and Gibson T. Osteonecrosis of the femoral head resulting from excessive corticosteroid nasal spray use. J. Clin. Rheumatol. 10 1 (2004) 45-47
91. Nasser S.M., and Ewan P.W. Lesson of the week: depot corticosteroid treatment for hay fever causing avascular necrosis of both hips. BMJ 322 7302 (2001) 1589-1591
92. Spencer C., Smith P., Rafla N., and Weatherell R. Corticosteroids in pregnancy and osteonecrosis of the femoral head. Obstet. Gynecol. 94 5 Part 2 (1999) 848
93. Talamo G., Angtuaco E., Walker R.C., Dong L., Miceli M.H., Zangari M., et al. Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy. J. Clin. Oncol. 23 22 (2005) 5217-5223
94. Macdonald A.G., and Bissett J.D. Avascular necrosis of the femoral head in patients with prostate cancer treated with cyproterone acetate and radiotherapy. Clin. Oncol. (R. Coll. Radiol.) 13 2 (2001) 135-137
95. Dawson L.K., Nussey F., Oliver T.B., Marks R.C., and Leonard R.C. Osteonecrosis of the femoral head following adjuvant chemotherapy for breast cancer. Breast. 10 5 (2001) 447-449
96. Freeman H.J., and Kwan W.C. Brief report: non-corticosteroid-associated osteonecrosis of the femoral heads in two patients with inflammatory bowel disease. N. Engl. J. Med. 329 18 (1993) 1314-1316
97. Koller E., Mann M., Malozowski S., Bacsanyi J., and Gibert C. Aseptic necrosis in HIV seropositive patients: a possible etiologic role for megestrol acetate. AIDS Patient Care STDS 14 8 (2000) 405-410
98. Scribner A.N., Troia-Cancio P.V., Cox B.A., Marcantonio D., Hamid F., Keiser P., et al. Osteonecrosis in HIV: a case-control study. J. Acquir. Immune Defic. Syndr. 25 1 (2000) 19-25
99. Schulte C.M., and Beelen D.W. Avascular osteonecrosis after allogeneic hematopoietic stem-cell transplantation: diagnosis and gender matter. Transplantation 78 7 (2004) 1055-1063
100. Pengde K., Fuxing P., Bin S., Jing Y., and Jingqiu C. Lovastatin inhibits adipogenesis and prevents osteonecrosis in steroid-treated rabbits. Joint Bone Spine 5 6 (2008) 696-701
101. Motomura G., Yamamoto T., Miyanishi K., Jingushi S., and Iwamoto Y. Combined effects of an anticoagulant and a lipid-lowering agent on the prevention of steroid-induced osteonecrosis in rabbits. Arthritis Rheum. 50 10 (2004) 3387-3391