International Orthopaedics

, Volume 43, Issue 3, pp 519–530 | Cite as

Osteonecrosis of the femoral head: genetic basis

  • Tracy WangEmail author
  • Bouziane Azeddine
  • Wayne Mah
  • Edward J. Harvey
  • David Rosenblatt
  • Chantal SéguinEmail author



Genetic factors and hereditary forms of osteonecrosis of the femoral head (ONFH) have been elucidated through genetic association studies. The significance of these cases is that they suggest an alternative hypothesis to the development of the disease. This review presents a summary of single nucleotide polymorphisms (SNPs) and other genetic mutation variations found in association with ONFH, including our recent identification of a novel mutation in the transient receptor potential vanilloid 4 (TRPV4) gene in association with inherited ONFH. The purpose of this review is to consolidate and categorize genetic linkages according to physiological pathways.


A systematic review of literature from PubMed and Google Scholar was undertaken with a focus on genetic linkages and hereditary case studies of the disease. Recent genetic analysis studies published after 2007 were the focus of genetic linkages in non-hereditary cases.


The summary of these genetic findings identifies biological processes believed to be involved in the development of ONFH, which include circulation, steroid metabolism, immunity, and the regulation of bone formation.


Taken together, these associations may lead to new pathways of bone repair and remodeling while opening new avenues for therapeutic targets. Knowledge of genetic variations could help identify individuals considered to be at higher risk of developing ONFH and prevent the multiple hit effect.


Osteonecrosis of the femoral head Polymorphisms Coagulation defects Steroids Immunity Hereditary ONFH TRPV4 



adenosine triphosphate-binding cassette B1


angiotensin I converting enzyme


annexin A2


apoliprotein B


avascular necrosis


Bone morphogenetic protein




CREB-binding protein


Collagen 2 aplha 1


C-terminal domain of RNA polymerase II subunit A, phosphatase of subunit 1


cytochrome P450, family 27, subfamily C, polypeptide 1


endothelial nitric oxide synthase


Glutamate Receptor, Ionotropic, N-Methyl-D-Aspartate 3A


Insulin-like growth factors


Insulin-like growth factor binding protein 3


Insulin-like growth factors binding protein




Kinase insert domain receptor


Legg-Calvé-Perthes disease


Multidrug resistance 1


magnetic resonance imaging


5, 10-methylenetetrahydrofolate reductase


Neuropilin 1


osteonecrosis of the femoral head


Plasminogen activator inhibitor-1




tissue plasminogen activator


paraoxonase 1


single nucleotide polymorphism


Sterol regulatory element-binding transcription factor 1


Sterol regulatory element-binding transcription factor 2




Tissue factor pathway inhibitor


Transforming growth factor


Tumor necrosis factor


Transient receptor potential vanilloid 4


vitamin D receptor


Vascular endothelial growth factor C



The authors gratefully acknowledge Dr. Terry Chow for reviewing the manuscript. This work was supported by awards to C. Séguin from the Fonds de la Recherche en Santé du Québec (FRQ-S) and from the Montreal General Hospital Foundation. C. Séguin is also supported by awards from the Canadian and US Leukemia & Lymphoma Societies.

Authors’ contributions

All authors read and approved the final manuscript. TW performed the literature search and participated in writing the first draft, BA finalized the literature search and participated in writing of the manuscript, finalizing the last version. TW and BA participated equally to this manuscript. EJH and DR helped to draft the manuscript and made an extensive revision. CS participated in the design of the review, its coordination and helped to draft the manuscript and finalizing the last version.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Larson E, Jones LC, Goodman SB, Koo KH, Cui Q (2018) Early-stage osteonecrosis of the femoral head: where are we and where are we going in year 2018? Int Orthop.
  2. 2.
    Kerachian MA, Harvey EJ, Cournoyer D, Chow TY, Seguin C (2006) Avascular necrosis of the femoral head: vascular hypotheses. Endothelium 13(4):237–244. Google Scholar
  3. 3.
    Mont MA, Cherian JJ, Sierra RJ, Jones LC, Lieberman JR (2015) Nontraumatic osteonecrosis of the femoral head: where do we stand today? A ten-year update. J Bone Joint Surg Am 97(19):1604–1627. Google Scholar
  4. 4.
    Zalavras CG, Lieberman JR (2014) Osteonecrosis of the femoral head: evaluation and treatment. J Am Acad Orthop Surg 22(7):455–464. Google Scholar
  5. 5.
    Chen WM, Liu YF, Lin MW, Chen IC, Lin PY, Lin GL, Jou YS, Lin YT, Fann CS, Wu JY, Hsiao KJ, Tsai SF (2004) Autosomal dominant avascular necrosis of femoral head in two Taiwanese pedigrees and linkage to chromosome 12q13. Am J Hum Genet 75(2):310–317. Google Scholar
  6. 6.
    Su P, Li R, Liu S, Zhou Y, Wang X, Patil N, Mow CS, Mason JC, Huang D, Wang Y (2008) Age at onset-dependent presentations of premature hip osteoarthritis, avascular necrosis of the femoral head, or Legg-Calve-Perthes disease in a single family, consequent upon a p.Gly1170Ser mutation of COL2A1. Arthritis Rheum 58(6):1701–1706. Google Scholar
  7. 7.
    Hadjigeorgiou G, Dardiotis E, Dardioti M, Karantanas A, Dimitroulias A, Malizos K (2008) Genetic association studies in osteonecrosis of the femoral head: mini review of the literature. Skelet Radiol 37(1):1–7. Google Scholar
  8. 8.
    Mah W, Sonkusare SK, Wang T, Azeddine B, Pupavac M, Carrot-Zhang J, Hong K, Majewski J, Harvey EJ, Russell L, Chalk C, Rosenblatt DS, Nelson MT, Seguin C (2016) Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head. J Med Genet.
  9. 9.
    Liu YF, Chen WM, Lin YF, Yang RC, Lin MW, Li LH, Chang YH, Jou YS, Lin PY, Su JS, Huang SF, Hsiao KJ, Fann CS, Hwang HW, Chen YT, Tsai SF (2005) Type II collagen gene variants and inherited osteonecrosis of the femoral head. N Engl J Med 352(22):2294–2301. Google Scholar
  10. 10.
    Kannu P, O'Rielly DD, Hyland JC, Kokko LA (2011) Avascular necrosis of the femoral head due to a novel C propeptide mutation in COL2A1. Am J Med Genet A 155A(7):1759–1762. Google Scholar
  11. 11.
    Miyamoto Y, Matsuda T, Kitoh H, Haga N, Ohashi H, Nishimura G, Ikegawa S (2007) A recurrent mutation in type II collagen gene causes Legg-Calve-Perthes disease in a Japanese family. Hum Genet 121(5):625–629. Google Scholar
  12. 12.
    Su P, Zhang L, Peng Y, Liang A, Du K, Huang D (2010) A histological and ultrastructural study of femoral head cartilage in a new type II collagenopathy. Int Orthop 34(8):1333–1339. Google Scholar
  13. 13.
    Darby WG, Grace MS, Baratchi S, McIntyre P (2016) Modulation of TRPV4 by diverse mechanisms. Int J Biochem Cell Biol 78:217–228. Google Scholar
  14. 14.
    Urbaniak JR, Harvey EJ (1998) Revascularization of the femoral head in osteonecrosis. J Am Acad Orthop Surg 6(1):44–54Google Scholar
  15. 15.
    Seguin C, Abid MR, Spokes KC, Schoots IG, Brkovic A, Sirois MG, Aird WC (2008) Priming effect of homocysteine on inducible vascular cell adhesion molecule-1 expression in endothelial cells. Biomed Pharmacother 62(6):395–400. Google Scholar
  16. 16.
    Shang XF, Su H, Chang WW, Wang CC, Han Q, Xu ZW (2012) Association between MTHFR C677T polymorphism and osteonecrosis of the femoral head: a meta-analysis. Mol Biol Rep 39(6):7089–7094. Google Scholar
  17. 17.
    Chai W, Zhang Z, Ni M, Geng P, Lian Z, Zhang G, Shi LL, Chen J (2015) Genetic association between methylenetetrahydrofolate reductase gene polymorphism and risk of osteonecrosis of the femoral head. Biomed Res Int 2015:196495. Google Scholar
  18. 18.
    Castoldi E, Rosing J (2004) Factor V Leiden: a disorder of factor V anticoagulant function. Curr Opin Hematol 11(3):176–181Google Scholar
  19. 19.
    Shang X, Luo Z, Li X, Hu F, Zhao Q, Zhang W (2013) Meta-analysis of Factor V Leiden G1691A polymorphism and osteonecrosis of femoral head susceptibility. Biomed Rep 1(4):594–598. Google Scholar
  20. 20.
    Gagala J, Buraczynska M, Mazurkiewicz T, Ksiazek A (2013) Prevalence of genetic risk factors related with thrombophilia and hypofibrinolysis in patients with osteonecrosis of the femoral head in Poland. BMC Musculoskelet Disord 14:264. Google Scholar
  21. 21.
    Jern C, Ladenvall P, Wall U, Jern S (1999) Gene polymorphism of t-PA is associated with forearm vascular release rate of t-PA. Arterioscler Thromb Vasc Biol 19(2):454–459Google Scholar
  22. 22.
    Munoz-Valle JF, Ruiz-Quezada SL, Oregon-Romero E, Navarro-Hernandez RE, Castaneda-Saucedo E, De la Cruz-Mosso U, Illades-Aguiar B, Leyva-Vazquez MA, Castro-Alarcon N, Parra-Rojas I (2012) PAI-1 mRNA expression and plasma level in rheumatoid arthritis: relationship with 4G/5G PAI-1 polymorphism. Rheumatol Int 32(12):3951–3956. Google Scholar
  23. 23.
    Liang XN, Xie L, Cheng JW, Tan Z, Yao J, Liu Q, Su W, Qin X, Zhao JM (2013) Association between PAI-1 4G/5G polymorphisms and osteonecrosis of femoral head: a meta-analysis. Thromb Res 132(2):158–163. Google Scholar
  24. 24.
    Li Y, Liu FX, Yuan C, Meng L (2017) Association between plasminogen activator inhibitor gene polymorphisms and osteonecrosis of the femoral head susceptibility: a case-control study. Medicine (Baltimore) 96(42):e7047. Google Scholar
  25. 25.
    Dai XL, Hong JM, Oh B, Cho YS, Lee JY, Park EK, Kim CY, Kim SY, Kim TH (2008) Association analysis of tissue factor pathway inhibitor polymorphisms and haplotypes with osteonecrosis of the femoral head in the Korean population. Mol Cells 26(5):490–495Google Scholar
  26. 26.
    Hadjigeorgiou GM, Malizos K, Dardiotis E, Aggelakis K, Dardioti M, Zibis A, Dimitroulias A, Scarmeas N, Tsezou A, Karantanas A (2007) Paraoxonase 1 gene polymorphisms in patients with osteonecrosis of the femoral head with and without cerebral white matter lesions. J Orthop Res 25(8):1087–1093. Google Scholar
  27. 27.
    Wang Z, Zhang Y, Kong X, Li S, Hu Y, Wang R, Li Y, Lu C, Lin N, Chen W (2013) Association of a polymorphism in PON-1 gene with steroid-induced osteonecrosis of femoral head in Chinese Han population. Diagn Pathol 8:186. Google Scholar
  28. 28.
    Li JM, Li Y, Wang L (2017) The genetic association between PON1 polymorphisms and osteonecrosis of femoral head: a case-control study. Medicine (Baltimore) 96(42):e8198. Google Scholar
  29. 29.
    Lee HJ, Choi SJ, Hong JM, Lee WK, Baek JI, Kim SY, Park EK, Kim SY, Kim TH, Kim UK (2009) Association of a polymorphism in the intron 7 of the SREBF1 gene with osteonecrosis of the femoral head in Koreans. Ann Hum Genet 73(1):34–41. Google Scholar
  30. 30.
    Song Y, Du ZW, Li QJ, Zhang GZ, Wang LL, Wu N, Wang JC, Gao ZL (2012) Association of sterol regulatory element binding protein 2 and insulin-like growth factor binding protein 3 genetic polymorphisms with avascular necrosis of the femoral head in the Chinese population. Chin Med J 125(22):4037–4043Google Scholar
  31. 31.
    Tsukada T, Yokoyama K, Arai T, Takemoto F, Hara S, Yamada A, Kawaguchi Y, Hosoya T, Igari J (1998) Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. Biochem Biophys Res Commun 245(1):190–193. Google Scholar
  32. 32.
    Koo KH, Lee JS, Lee YJ, Kim KJ, Yoo JJ, Kim HJ (2006) Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis. J Orthop Res 24(8):1722–1728. Google Scholar
  33. 33.
    Song GG, Lee YH (2017) Association of eNOS polymorphisms with susceptibility to osteonecrosis of the femur head : a meta-analysis. Z Rheumatol 76(3):267–273. Google Scholar
  34. 34.
    Hong JM, Kim TH, Kim HJ, Park EK, Yang EK, Kim SY (2010) Genetic association of angiogenesis- and hypoxia-related gene polymorphisms with osteonecrosis of the femoral head. Exp Mol Med 42(5):376–385. Google Scholar
  35. 35.
    Kannu P, Irving M, Aftimos S, Savarirayan R (2011) Two novel COL2A1 mutations associated with a Legg-Calve-Perthes disease-like presentation. Clin Orthop Relat Res 469(6):1785–1790. Google Scholar
  36. 36.
    Chang JD, Hur M, Lee SS, Yoo JH, Lee KM (2008) Genetic background of nontraumatic osteonecrosis of the femoral head in the Korean population. Clin Orthop Relat Res 466(5):1041–1046. Google Scholar
  37. 37.
    Gagala J, Buraczynska M, Mazurkiewicz T, Ksiazek A (2013) Endothelial nitric oxide synthase gene intron 4 polymorphism in non-traumatic osteonecrosis of the femoral head. Int Orthop 37(7):1381–1385. Google Scholar
  38. 38.
    Lee YJ, Lee JS, Kang EH, Lee YK, Kim SY, Song YW, Koo KH (2012) Vascular endothelial growth factor polymorphisms in patients with steroid-induced femoral head osteonecrosis. J Orthop Res 30(1):21–27. Google Scholar
  39. 39.
    Pandey S, Ranjan R, Pandey S, Mishra RM, Seth T, Saxena R (2012) Effect of ANXA2 gene single nucleotide polymorphism (SNP) on the development of osteonecrosis in Indian sickle cell patient: a PCR-RFLP approach. Indian J Exp Biol 50(7):455–458Google Scholar
  40. 40.
    Karol SE, Yang W, Van Driest SL, Chang TY, Kaste S, Bowton E, Basford M, Bastarache L, Roden DM, Denny JC, Larsen E, Winick N, Carroll WL, Cheng C, Pei D, Fernandez CA, Liu C, Smith C, Loh ML, Raetz EA, Hunger SP, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Mattano LA Jr, Relling MV (2015) Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood.
  41. 41.
    Chen J, Liu W, Cao Y, Zhang X, Guo Y, Zhu Y, Li J, Du J, Jin T, Wang G, Wang J (2017) MMP-3 and MMP-8 single-nucleotide polymorphisms are related to alcohol-induced osteonecrosis of the femoral head in Chinese males. Oncotarget 8(15):25177–25188. Google Scholar
  42. 42.
    Du J, Liu W, Jin T, Zhao Z, Bai R, Xue H, Chen J, Sun M, Zhang X, Wang G, Wang J (2016) A single-nucleotide polymorphism in MMP9 is associated with decreased risk of steroid-induced osteonecrosis of the femoral head. Oncotarget 7(42):68434–68441. Google Scholar
  43. 43.
    Li Y, Wang Y, Guo Y, Wang Q, Ouyang Y, Cao Y, Jin T, Wang J (2016) OPG and RANKL polymorphisms are associated with alcohol-induced osteonecrosis of the femoral head in the north area of China population in men. Medicine (Baltimore) 95(25):e3981. Google Scholar
  44. 44.
    Kim TH, Hong JM, Oh B, Cho YS, Lee JY, Kim HL, Lee JE, Ha MH, Park EK, Kim SY (2008) Association of polymorphisms in the Interleukin 23 receptor gene with osteonecrosis of femoral head in Korean population. Exp Mol Med 40(4):418–426. Google Scholar
  45. 45.
    Kuribayashi M, Fujioka M, Takahashi KA, Arai Y, Hirata T, Nakajima S, Yoshimura N, Satomi Y, Nishino H, Kondo K, Fukushima W, Hirota Y, Kubo T (2008) Combination analysis of three polymorphisms for predicting the risk for steroid-induced osteonecrosis of the femoral head. J Orthop Sci 13(4):297–303. Google Scholar
  46. 46.
    Kim TH, Hong JM, Oh B, Cho YS, Lee JY, Kim HL, Shin ES, Lee JE, Park EK, Kim SY (2008) Genetic association study of polymorphisms in the catalase gene with the risk of osteonecrosis of the femoral head in the Korean population. Osteoarthr Cartil 16(9):1060–1066. Google Scholar
  47. 47.
    Liu Y, Zhang Z, Liu S, Su X, Zhou S (2015) Association between VEGF -634G/C polymorphism and osteonecrosis of the femoral head susceptibility: a meta analysis. Int J Clin Exp Med 8(7):10979–10985Google Scholar
  48. 48.
    Hernigou P, Daltro G (2014) Osteonecrosis in Sickle-Cell Disease. In: Koo K-H, Mont MA, Jones LC (eds) Osteonecrosis. Springer Berlin Heidelberg, Berlin, pp 125–131. Google Scholar
  49. 49.
    Daltro G, Franco BA, Faleiro TB, Rosario DAV, Daltro PB, Fortuna V (2018) Osteonecrosis in sickle cell disease patients from Bahia, Brazil: a cross-sectional study. Int Orthop 42(7):1527–1534. Google Scholar
  50. 50.
    Gurzu S, Turdean SG, Pop ST, Zazgyva A, Roman CO, Opris M, Jung I (2017) Different synovial vasculogenic profiles of primary, rapidly destructive and osteonecrosis-induced hip osteoarthritis. An immunohistochemistry study. Int Orthop 41(6):1107–1112. Google Scholar
  51. 51.
    Kabata T, Matsumoto T, Yagishita S, Wakayama T, Iseki S, Tomita K (2008) Vascular endothelial growth factor in rabbits during development of corticosteroid-induced osteonecrosis: a controlled experiment. J Rheumatol 35(12):2383–2390. Google Scholar
  52. 52.
    Varoga D, Drescher W, Pufe M, Groth G, Pufe T (2009) Differential expression of vascular endothelial growth factor in glucocorticoid-related osteonecrosis of the femoral head. Clin Orthop Relat Res 467(12):3273–3282. Google Scholar
  53. 53.
    Asano T, Takahashi KA, Fujioka M, Inoue S, Satomi Y, Nishino H, Tanaka T, Hirota Y, Takaoka K, Nakajima S, Kubo T (2003) Genetic analysis of steroid-induced osteonecrosis of the femoral head. J Orthop Sci 8(3):329–333. Google Scholar
  54. 54.
    He N, Li S, Liu H (2009) High-throughput SNP detection based on PCR amplification on magnetic nanoparticles using dual-color hybridization. Methods Mol Biol 578:393–402. Google Scholar
  55. 55.
    Zhang Y, Kong X, Wang R, Li S, Niu Y, Zhu L, Chen W, Lin N (2014) Genetic association of the P-glycoprotein gene ABCB1 polymorphisms with the risk for steroid-induced osteonecrosis of the femoral head in Chinese population. Mol Biol Rep 41(5):3135–3146. Google Scholar
  56. 56.
    Han N, Yan Z, Guo CA, Shen F, Liu J, Shi Y, Zhang Z (2010) Effects of p-glycoprotein on steroid-induced osteonecrosis of the femoral head. Calcif Tissue Int 87(3):246–253. Google Scholar
  57. 57.
    Krupoves A, Mack D, Seidman E, Deslandres C, Amre D (2011) Associations between variants in the ABCB1 (MDR1) gene and corticosteroid dependence in children with Crohn's disease. Inflamm Bowel Dis 17(11):2308–2317. Google Scholar
  58. 58.
    Zhou Z, Hua Y, Liu J, Zuo D, Wang H, Chen Q, Zheng L, Cai Z (2015) Association of ABCB1/MDR1 polymorphisms in patients with glucocorticoid-induced osteonecrosis of the femoral head: evidence for a meta-analysis. Gene 569(1):34–40. Google Scholar
  59. 59.
    Zhang Y, Xie H, Zhao D, Wang B, Yang L, Meng Q (2017) Association of ABCB1 C3435T polymorphism with the susceptibility to osteonecrosis of the femoral head: a meta-analysis. Medicine (Baltimore) 96(20):e6049. Google Scholar
  60. 60.
    Samara S, Kollia P, Dailiana Z, Chassanidis C, Papatheodorou L, Koromila T, Malizos KN (2012) Predictive role of cytokine gene polymorphisms for the development of femoral head osteonecrosis. Dis Markers 33(4):215–221. Google Scholar
  61. 61.
    Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13(5):715–725Google Scholar
  62. 62.
    Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW (2002) A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168(11):5699–5708Google Scholar
  63. 63.
    Wang Y, Yang X, Shi J, Zhao Y, Pan L, Zhou J, Wang G, Wang J (2017) Combination analysis of NOS3, ABCB1 and IL23R polymorphisms with alcohol-induced osteonecrosis of the femoral head risk in Chinese males. Oncotarget 8(20):33770–33778. Google Scholar
  64. 64.
    Zheng L, Wang W, Ni J, Li Z, Xiao T, Zhang Q, Mao X, He A (2014) Plasma interleukin 33 level in patients with osteonecrosis of femoral head: an alarmin for osteonecrosis of the femoral head? J Investig Med 62(3):635–637. Google Scholar
  65. 65.
    Ma J, Guo W, Li Z, Wang B, Li S, Wang P (2017) Hip osteonecrosis is associated with increased plasma IL-33 level. Mediat Inflamm 2017:1732638. Google Scholar
  66. 66.
    Dai JC, He P, Chen X, Greenfield EM (2006) TNFalpha and PTH utilize distinct mechanisms to induce IL-6 and RANKL expression with markedly different kinetics. Bone 38(4):509–520. Google Scholar
  67. 67.
    El-Tahan RR, Ghoneim AM, El-Mashad N (2016) TNF-alpha gene polymorphisms and expression. Springerplus 5(1):1508. Google Scholar
  68. 68.
    Wei BF, Feng Z, Wei W, Chen X (2017) Associations of TNF-alpha -238 A/G and IL-10 -1082 G/A genetic polymorphisms with the risk of NONFH in the Chinese population. J Cell Biochem.
  69. 69.
    Peng Y, Liu Y, Huang D, Huang W, Shao Z (2018) Association of TNF-alpha-308(G/A) and −238(G/A) polymorphisms with non-traumatic osteonecrosis of the femoral head risks: a meta-analysis. Int Orthop.
  70. 70.
    Ulug P, Vasavda N, Awogbade M, Cunningham J, Menzel S, Thein SL (2009) Association of sickle avascular necrosis with bone morphogenic protein 6. Ann Hematol 88(8):803–805. Google Scholar
  71. 71.
    Dar AA, Majid S, Nosrati M, de Semir D, Federman S, Kashani-Sabet M (2010) Functional modulation of IGF-binding protein-3 expression in melanoma. J Invest Dermatol 130(8):2071–2079. Google Scholar
  72. 72.
    Nadeau M, Seguin C, Theodoropoulos JS, Harvey EJ (2007) Short term clinical outcome of a porous tantalum implant for the treatment of advanced osteonecrosis of the femoral head. Mcgill J Med 10(1):4–10Google Scholar
  73. 73.
    Kuroda Y, Matsuda S, Akiyama H (2016) Joint-preserving regenerative therapy for patients with early-stage osteonecrosis of the femoral head. Inflamm Regen 36:4. Google Scholar
  74. 74.
    Kuroda Y, Asada R, So K, Yonezawa A, Nankaku M, Mukai K, Ito-Ihara T, Tada H, Yamamoto M, Murayama T, Morita S, Tabata Y, Yokode M, Shimizu A, Matsuda S, Akiyama H (2016) A pilot study of regenerative therapy using controlled release of recombinant human fibroblast growth factor for patients with pre-collapse osteonecrosis of the femoral head. Int Orthop 40(8):1747–1754. Google Scholar
  75. 75.
    Andriolo L, Merli G, Tobar C, Altamura SA, Kon E, Filardo G (2018) Regenerative therapies increase survivorship of avascular necrosis of the femoral head: a systematic review and meta-analysis. Int Orthop 42(7):1689–1704. Google Scholar
  76. 76.
    Brakspear KS, Mason DJ (2012) Glutamate signaling in bone. Front Endocrinol (Lausanne) 3:97. Google Scholar

Copyright information

© SICOT aisbl 2018

Authors and Affiliations

  • Tracy Wang
    • 1
    Email author
  • Bouziane Azeddine
    • 1
  • Wayne Mah
    • 1
  • Edward J. Harvey
    • 2
  • David Rosenblatt
    • 3
  • Chantal Séguin
    • 1
    • 4
    • 5
    Email author
  1. 1.Vascular Biology Research lab, Research Institute (RI) McGill University Health CentreC9 Montreal General HospitalQCCanada
  2. 2.Department Surgery, Division Orthopaedic Surgery, McGill University Health CentreB5 Montreal General HospitalQCCanada
  3. 3.Department of Human GeneticsMcGill UniversityQuebecCanada
  4. 4.Department of Medicine, Division of Hematology and OncologyMcGill University Health CentreQuebecCanada
  5. 5.Glen Site, Cedars Cancer CentreMcGill University Health CentreQuebecCanada

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