Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 1/2011

01-08-2011

Current Concepts on the Pathogenesis and Natural History of Steroid-Induced Osteonecrosis

Authors: Christian Powell, Christopher Chang, M. Eric Gershwin

Published in: Clinical Reviews in Allergy & Immunology | Issue 1/2011

Login to get access

Abstract

The pathophysiology of non-traumatic osteonecrosis is more complex than that of traumatic osteonecrosis, and corticosteroid-induced osteonecrosis presents the greatest 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, and our understanding of the pathogenesis must be able to explain why some patients are at greater risk than others. Identification of genetic variants that convey additional risk will also help to personalize the way we deliver care, both in the prevention and treatment of osteonecrosis. Further understanding of the intricate immunologic and genetic pathways contributing to osteonecrosis is at the forefront of research and may soon lead to viable and less invasive non-surgical therapeutic strategies.
Literature
1.
Powell C, Chang C, Naguwa SM, Cheema G, Gershwin ME (2010) Steroid induced osteonecrosis: an analysis of steroid dosing risk. Autoimmun Rev 9:721–743PubMedCrossRef
2.
Chang C, Greenspan A, Gershwin ME. Osteonecrosis. In Firestein GS, Budd RC, Harris ED, McInnes IB, Ruddy S, Sergent JS (2009) Textbook of Rheumatology, 8th Edition, Saunders, Philadelphia, pp 1611–1628
3.
Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME (2002) Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 32:94–124PubMed
4.
Spencer JD, Brookes M (1988) Avascular necrosis and the blood supply of the femoral head. Clin Orthop Relat Res 235:127–140PubMed
5.
Jacobs B (1978) Epidemiology of traumatic and nontraumatic osteonecrosis. Clin Orthop Relat Res 130:51–67PubMed
6.
Atsumi T, Kuroki Y (1992) Role of impairment of blood supply of the femoral head in the pathogenesis of idiopathic osteonecrosis. Clin Orthop Relat Res 277:22–30PubMed
7.
Jones LC, Mont MA, Le TB, Petri M, Hungerford DS, Wang P, Glueck CJ (2003) Procoagulants and osteonecrosis. J Rheumatol 30:783–791PubMed
8.
Jones JP Jr (1999) Coagulopathies and osteonecrosis. Acta Orthop Belg 65(Suppl 1):5–8PubMed
9.
Chandler FA (1948) Coronary disease of the hip. J Int Coll Surg 11:34–36PubMed
10.
Chandler FA (1949) Coronary disease of the hip. Clin Orthop Relat Res 2001:7–10
11.
Silvestrini G, Mocetti P, Ballanti P, Di Grezia R, Bonucci E (1999) Cytochemical demonstration of the glucocorticoid receptor in skeletal cells of the rat. Endocr Res 25:117–128PubMed
12.
Dempster DW, Moonga BS, Stein LS, Horbert WR, Antakly T (1997) Glucocorticoids inhibit bone resorption by isolated rat osteoclasts by enhancing apoptosis. J Endocrinol 154:397–406PubMedCrossRef
13.
Liesegang P, Romalo G, Sudmann M, Wolf L, Schweikert HU (1994) Human osteoblast-like cells contain specific, saturable, high-affinity glucocorticoid, androgen, estrogen, and 1 alpha, 25-dihydroxycholecalciferol receptors. J Androl 15:194–199PubMed
14.
Yoshioka T, Sato B, Matsumoto K, Ono K (1980) Steroid receptors in osteoblasts. Clin Orthop Relat Res 148:297–303PubMed
15.
Kerachian MA, Seguin C, Harvey EJ (2009) Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol 114:121–128PubMedCrossRef
16.
Calder JD, Buttery L, Revell PA, Pearse M, Polak JM (2004) Apoptosis—a significant cause of bone cell death in osteonecrosis of the femoral head. J Bone Joint Surg Br 86:1209–1213PubMedCrossRef
17.
Weinstein RS, Nicholas RW, Manolagas SC (2000) Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab 85:2907–2912PubMedCrossRef
18.
Kogianni G, Mann V, Ebetino F, Nuttall M, Nijweide P, Simpson H, Noble B (2004) Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis. Life Sci 75:2879–2895PubMedCrossRef
19.
Weinstein RS, Chen JR, Powers CC, Stewart SA, Landes RD, Bellido T, Jilka RL et al (2002) Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids. J Clin Invest 109:1041–1048PubMed
20.
Kawai K, Tamaki A, Hirohata K (1985) Steroid-induced accumulation of lipid in the osteocytes of the rabbit femoral head. A histochemical and electron microscopic study. J Bone Joint Surg Am 67:755–763PubMed
21.
Boskey AL, Raggio CL, Bullough PG, Kinnett JG (1983) Changes in the bone tissue lipids in persons with steroid- and alcohol-induced osteonecrosis. Clin Orthop Relat Res 172:289–295PubMed
22.
Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282PubMedCrossRef
23.
Wang GJ, Cui Q, Balian G (2000) The Nicolas Andry award. The pathogenesis and prevention of steroid-induced osteonecrosis Clin Orthop Relat Res 370:295–310
24.
Aspenberg P (2006) Osteonecrosis of the jaw: what do bisphosphonates do? Expert Opin Drug Saf 5:743–745PubMedCrossRef
25.
Assael LA (2009) Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaws: clinical findings, assessment of risks, and preventive strategies. J Oral Maxillofac Surg 67:35–43PubMedCrossRef
26.
Bilezikian JP (2006) Osteonecrosis of the jaw—do bisphosphonates pose a risk? N Engl J Med 355:2278–2281PubMedCrossRef
27.
Pendrys DG, Silverman SL (2008) Osteonecrosis of the jaws and bisphosphonates. Curr Osteoporos Rep 6:31–38PubMedCrossRef
28.
Walter C, Pabst A, Ziebart T, Klein M, Al-Nawas B. Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro. Oral Dis 2010 (In press)
29.
Harper RN, Moore MA, Marr MC, Watts LE, Hutchins PM (1978) Arteriolar rarefaction in the conjunctiva of human essential hypertensives. Microvasc Res 16:369–372PubMedCrossRef
30.
Kerachian MA, Harvey EJ, Cournoyer D, Chow TY, Seguin C (2006) Avascular necrosis of the femoral head: vascular hypotheses. Endothelium 13:237–244PubMedCrossRef
31.
Feng Y, Yang SH, Xiao BJ, et al (2010) Decreased in the number and function of circulation endothelial progenitor cells in patients with avascular necrosis of the femoral head. Bone 46:32–40
32.
Li YM, Wang SX, Gao HS, Wang JG, Wei CS, Chen LM, Hui WL et al (2004) Factors of avascular necrosis of femoral head and osteoporosis in SARS patients' convalescence. Zhonghua Yi Xue Za Zhi 84:1348–1353PubMed
33.
Jones JP Jr, Ramirez S, Doty SB (1993) The pathophysiologic role of fat in dysbaric osteonecrosis. Clin Orthop Relat Res 296:256–264PubMed
34.
Gray E, Thomas S, Mistry Y, Poole S (1996) Inhibition of tissue factor and cytokine release. Haemostasis 26(Suppl 1):92–95PubMed
35.
van Giezen JJ, Jansen JW (1992) Correlation of in vitro and in vivo decreased fibrinolytic activity caused by dexamethasone. Ann NY Acad Sci 667:199–201PubMedCrossRef
36.
Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C (2004) Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 141:47–56PubMed
37.
Boss JH, Misselevich I (2003) Osteonecrosis of the femoral head of laboratory animals: the lessons learned from a comparative study of osteonecrosis in man and experimental animals. Vet Pathol 40:345–354PubMedCrossRef
38.
Hirata T, Fujioka M, Takahashi KA, Asano T, Ishida M, Akioka K, Okamoto M et al (2007) Low molecular weight phenotype of Apo(a) is a risk factor of corticosteroid-induced osteonecrosis of the femoral head after renal transplant. J Rheumatol 34:516–522PubMed
39.
Ferrari P, Schroeder V, Anderson S, Kocovic L, Vogt B, Schiesser D, Marti HP et al (2002) Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients. Transplantation 74:1147–1152PubMedCrossRef
40.
Kang P, Shen B, Yang J, Pei F (2008) Circulating platelet-derived microparticles and endothelium-derived microparticles may be a potential cause of microthrombosis in patients with osteonecrosis of the femoral head. Thromb Res 123:367–373PubMedCrossRef
41.
Chotanaphuti T, Heebthamai D, Chuwong M, Kanchanaroek K (2009) The prevalence of thrombophilia in idiopathic osteonecrosis of the hip. J Med Assoc Thai 92(Suppl 6):S141–S146PubMed
42.
Glueck CJ, Freiberg RA, Boppana S, Wang P (2008) Thrombophilia, hypofibrinolysis, the eNOS T-786 C polymorphism, and multifocal osteonecrosis. J Bone Joint Surg Am 90:2220–2229PubMedCrossRef
43.
Glueck CJ, Freiberg RA, Wang P (2008) Heritable thrombophilia–hypofibrinolysis and osteonecrosis of the femoral head. Clin Orthop Relat Res 466:1034–1040PubMedCrossRef
44.
Seguin C, Kassis J, Busque L, Bestawros A, Theodoropoulos J, Alonso ML, Harvey EJ (2008) Non-traumatic necrosis of bone (osteonecrosis) is associated with endothelial cell activation but not thrombophilia. Rheumatology (Oxford) 47:1151–1155CrossRef
45.
Arlet J, Ficat P, Lartigue G, Tran MA (1972) Clinical research on intraosseous pressure in the upper femoral metaphysis and epiphysis in humans. Application to the diagnosis of ischemia and necrosis. Rev Rhum Mal Osteo-artic 39:717–723
46.
Wang KZ, Mao LZ, Hu CG (1994) Experimental study on mechanism of steroid-induced avascular necrosis of femoral head. Zhonghua Wai Ke Za Zhi 32:515–517PubMed
47.
Wang KZ, Wang CS, Wu YG, Chen H (2006) Changes of vessel in steroid-induced osteonecrosis of femoral head: experimental study of rabbits. Zhonghua Yi Xue Za Zhi 86:2024–2027PubMed
48.
Wang ZX, Yang ZX (1985) Experimental observations on the biological features and pathogenicity of Thelazia callipaeda parasitized in rabbits. Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 3:128–130PubMed
49.
Welch RD, Johnston CE 2nd, Waldron MJ, Poteet B (1993) Bone changes associated with intraosseous hypertension in the caprine tibia. J Bone Joint Surg Am 75:53–60PubMed
50.
Saito S, Ohzono K, Ono K (1992) Early arteriopathy and postulated pathogenesis of osteonecrosis of the femoral head. The intracapital arterioles Clin Orthop Relat Res 277:98–110
51.
Yang C, Yang S, Du J, Li J, Xu W, Xiong Y (2003) Experimental study of vascular endothelial growth factor gene therapy for avascular necrosis of the femoral head. J Huazhong Univ Sci Technolog Med Sci 23(297–299):316
52.
Li X, Jin L, Cui Q, Wang GJ, Balian G (2005) Steroid effects on osteogenesis through mesenchymal cell gene expression. Osteoporos Int 16:101–108PubMedCrossRef
53.
Harada I (1992) The effects of glucocorticoids on angiogenesis in vitro. Nippon Seikeigeka Gakkai Zasshi 66:763–770PubMed
54.
Wolff JE, Guerin C, Laterra J, Bressler J, Indurti RR, Brem H, Goldstein GW (1993) Dexamethasone reduces vascular density and plasminogen activator activity in 9 L rat brain tumors. Brain Res 604:79–85PubMedCrossRef
55.
56.
Ichiseki T, Matsumoto T, Nishino M, Kaneuji A, Katsuda S (2004) Oxidative stress and vascular permeability in steroid-induced osteonecrosis model. J Orthop Sci 9:509–515PubMedCrossRef
57.
Ichiseki T, Kaneuji A, Katsuda S, Ueda Y, Sugimori T, Matsumoto T (2005) DNA oxidation injury in bone early after steroid administration is involved in the pathogenesis of steroid-induced osteonecrosis. Rheumatology (Oxford) 44:456–460CrossRef
58.
Ichiseki T, Matsumoto T (2006) Oxidative stress may underlie the sex differences seen in steroid-induced osteonecrosis models. Med Hypotheses 66:1256PubMedCrossRef
59.
Jaffe WL, Epstein M, Heyman N, Mankin HJ (1972) The effect of cortisone on femoral and humeral heads in rabbits. An experimental study. Clin Orthop Relat Res 82:221–228PubMedCrossRef
60.
Zhou Q, Li Q, Yang L, Liu F (2000) Changes of blood vessels in glucocorticoid-induced avascular necrosis of femoral head in rabbits. Zhonghua Wai Ke Za Zhi 38(212–215):213
61.
Chen XC, Weng J, Chen XQ, Du JZ, Zhu MP, Pan YQ, Liu M (2008) Relationships among magnetic resonance imaging, histological findings, and IGF-I in steroid-induced osteonecrosis of the femoral head in rabbits. J Zhejiang Univ Sci B 9:739–746PubMedCrossRef
62.
Cui Q, Wang GJ, Su CC, Balian G (1997) The Otto Aufranc Award. Lovastatin prevents steroid induced adipogenesis and osteonecrosis Clin Orthop Relat Res 344:8–19
63.
Wang GJ, Moga DB, Richemer WG, Sweet DE, Reger SI, Thompson RC (1978) Cortisone induced bone changes and its response to lipid clearing agents. Clin Orthop Relat Res 130:81–85PubMed
64.
Jones JP Jr (1985) Fat embolism and osteonecrosis. Orthop Clin North Am 16:595–633PubMed
65.
Motomura G, Yamamoto T, Irisa T, Miyanishi K, Nishida K, Iwamoto Y (2008) Dose effects of corticosteroids on the development of osteonecrosis in rabbits. J Rheumatol 35:2395–2399PubMedCrossRef
66.
Motomura G, Yamamoto T, Miyanishi K, Jingushi S, Iwamoto Y (2004) Combined effects of an anticoagulant and a lipid-lowering agent on the prevention of steroid-induced osteonecrosis in rabbits. Arthritis Rheum 50:3387–3391PubMedCrossRef
67.
Yamamoto T, Irisa T, Sugioka Y, Sueishi K (1997) Effects of pulse methylprednisolone on bone and marrow tissues: corticosteroid-induced osteonecrosis in rabbits. Arthritis Rheum 40:2055–2064PubMedCrossRef
68.
Motomura G, Yamamoto T, Miyanishi K, Kondo K, Hirota Y, Iwamoto Y (2008) Risk factors for developing osteonecrosis after prophylaxis in steroid-treated rabbits. J Rheumatol 35:2391–2394PubMedCrossRef
69.
Tokuhara Y, Wakitani S, Oda Y, Kaneshiro Y, Masada T, Kim M, Kadoya Y et al (2009) 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 Orthop Sci 14:794–800PubMedCrossRef
70.
Masada T, Iwakiri K, Oda Y, Kaneshiro Y, Iwaki H, Ohashi H, Takaoka K (2008) Increased hepatic cytochrome P4503A activity decreases the risk of developing steroid-induced osteonecrosis in a rabbit model. J Orthop Res 26:91–95PubMedCrossRef
71.
Kaneshiro Y, Oda Y, Iwakiri K, Masada T, Iwaki H, Hirota Y, Kondo K et al (2006) Low hepatic cytochrome P450 3A activity is a risk for corticosteroid-induced osteonecrosis. Clin Pharmacol Ther 80:396–402PubMedCrossRef
72.
Asano T, Takahashi KA, Fujioka M, Inoue S, Satomi Y, Nishino H, Tanaka T et al (2003) Genetic analysis of steroid-induced osteonecrosis of the femoral head. J Orthop Sci 8:329–333PubMedCrossRef
73.
Wang XY, Niu XH, Chen WH, Lin N, Song JN, Chen B, Jin H (2008) Effects of apolipoprotein A1 and B gene polymorphism on avascular necrosis of the femoral head in Chinese population. Zhongguo Gu Shang 21:99–102PubMed
74.
Asano T, Takahashi KA, Fujioka M, Inoue S, Ueshima K, Hirata T, Okamoto M et al (2004) Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects. Transplantation 77:220–225PubMedCrossRef
75.
Kim TH, Hong JM, Shin ES, Kim HJ, Cho YS, Lee JY, Lee SH et al (2009) Polymorphisms in the annexin gene family and the risk of osteonecrosis of the femoral head in the Korean population. Bone 45:125–131PubMedCrossRef
76.
Kim TH, Hong JM, Oh B, Cho YS, Lee JY, Kim HL, Lee JE et al (2008) Association of polymorphisms in the Interleukin 23 receptor gene with osteonecrosis of femoral head in Korean population. Exp Mol Med 40:418–426PubMedCrossRef
77.
Kenzora JE (1983) Ischemic necrosis of femoral head. Part I. Accumulative cell stress: a hypothesis for the etiology of idiopathic osteonecrosis. Instr Course Lect 32:242–252PubMed
78.
Kenzora JE (1985) Treatment of idiopathic osteonecrosis: the current philosophy and rationale. Orthop Clin North Am 16:717–725PubMed
Metadata
Title
Current Concepts on the Pathogenesis and Natural History of Steroid-Induced Osteonecrosis
Authors
Christian Powell
Christopher Chang
M. Eric Gershwin
Publication date
01-08-2011
Publisher
Humana Press Inc
Published in
Clinical Reviews in Allergy & Immunology / Issue 1/2011
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-010-8217-z

Other articles of this Issue 1/2011

Clinical Reviews in Allergy & Immunology 1/2011 Go to the issue

OriginalPaper

Atopy Risk in Infants and Children in Relation to Early Exposure to Fish, Oily Fish, or Long-Chain Omega-3 Fatty Acids: A Systematic Review

ReviewPaper

Intranasal Steroids in the Treatment of Allergy-Induced Rhinorrhea

OriginalPaper

Novel Challenges for the Allergist

ReviewPaper

Chemokines and Their Receptors in the Allergic Airway Inflammatory Process

ReviewPaper

Therapeutic Approaches in Hereditary Angioedema

OriginalPaper

Identification of European Allergy Patterns to the Allergen Families PR-10, LTP, and Profilin from Rosaceae Fruits
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits