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Osteonecrosis and Thrombophilia: Pathophysiology, Diagnosis, and Treatment

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Osteonecrosis of the Femoral Head

Abstract

We describe three patients: two women, ages 47 and 69, and a man, age 54, with Ficat stages I, II, and I–II primary osteonecrosis at entry. Coagulation tests revealed heterozygosity for the G20210A prothrombin gene mutation, resistance to activated protein C, and heterozygosity for the factor V Leiden mutation, respectively. In two patients, ages 47 and 54, exogenous testosterone appeared to interact with the prothrombin and factor V Leiden mutations, promoting onset of osteonecrosis. Testosterone was stopped. In all three cases, long-term anticoagulation (4, 13, and 10 years) completely relieved pain, there was no joint collapse, and the Ficat stages were unchanged or improved. In patients with primary osteonecrosis (Ficat stages I–II) and major gene thrombophilias, long-term anticoagulation for 4, 13, and 10 years as in our three patients can ameliorate pain, restore normal joint function, prevent joint collapse, and lead to stable or improved X-rays and MRIs, providing a medical approach to treatment of primary osteonecrosis.

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References

  1. Glueck CJ, Freiberg R, Tracy T, Stroop D, Wang P. Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis. Clin Orthop. 1997;334:43–56.

    Article  Google Scholar 

  2. Mannucci PM, Franchini M. Classic thrombophilic gene variants. Thromb Haemost. 2015;114:885–9.

    Article  PubMed  Google Scholar 

  3. Bjorkman A, Svensson PJ, Hillarp A, Burtscher IM, Runow A, Benoni G. Factor V leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin Orthop Relat Res. 2004;425:168–72.

    Article  Google Scholar 

  4. Glueck CJ, Riaz R, Prince M, Freiberg RA, Wang P. Testosterone therapy interacts with previously undiagnosed familial thrombophilia, facilitating development of osteonecrosis. Orthopedics. 2015;38:e1073–8.

    Article  PubMed  Google Scholar 

  5. Glueck CJ, Freiberg RA, Sieve L, Wang P. Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res. 2005;435:164–70.

    Article  Google Scholar 

  6. Glueck CJ, Freiberg RA, Wissman R, Wang P. Long term anticoagulation (4–16 years) stops progression of idiopathic hip osteonecrosis associated with familial thrombophilia. Adv Orthop. 2015;2015:138382.

    PubMed  PubMed Central  Google Scholar 

  7. Touma L, Filion KB, Atallah R, Eberg M, Eisenberg MJ. A meta-analysis of randomized controlled trials of the risk of bleeding with apixaban versus vitamin K antagonists. Am J Cardiol. 2015;115:533–41.

    Article  CAS  PubMed  Google Scholar 

  8. Wasserlauf G, Grandi SM, Filion KB, Eisenberg MJ. Meta-analysis of rivaroxaban and bleeding risk. Am J Cardiol. 2013;112:454–60.

    Article  CAS  PubMed  Google Scholar 

  9. Bloom BJ, Filion KB, Atallah R, Eisenberg MJ. Meta-analysis of randomized controlled trials on the risk of bleeding with dabigatran. Am J Cardiol. 2014;113:1066–74.

    Article  CAS  PubMed  Google Scholar 

  10. Freedman J, Glueck CJ, Prince M, Riaz R, Wang P. Testosterone, thrombophilia, thrombosis. Transl Res. 2015;165:537–48.

    Article  CAS  PubMed  Google Scholar 

  11. Williamson D, Brown K, Luddington R, Baglin C, Baglin T. Factor V Cambridge: a new mutation (Arg306-->Thr) associated with resistance to activated protein C. Blood. 1998;91:1140–4.

    CAS  PubMed  Google Scholar 

  12. Glueck CJ, Freiberg RA, Wang P. Medical treatment of osteonecrosis of the knee associated with thrombophilia-hypofibrinolysis. Orthopedics. 2014;37:e911–6.

    Article  PubMed  Google Scholar 

  13. Glueck CJ Freiberg RA, Wang P. Treatment of osteonecrosis of the hip and knee with enoxaparin. Osteonecrosis, ed Koo KH, Mont M, Jones L 2014;Chapter 32, pp 241–247, Berlin Springer.

    Google Scholar 

  14. Orth P, Anagnostakos K. Coagulation abnormalities in osteonecrosis and bone marrow edema syndrome. Orthopedics. 2013;36:290–300.

    Article  PubMed  Google Scholar 

  15. Glueck CJ, Freiberg RA, Wang P. Heritable thrombophilia-hypofibrinolysis and osteonecrosis of the femoral head. Clin Orthop Relat Res. 2008;466:1034–40.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop. 2001;386:19–33.

    Article  Google Scholar 

  17. Koo KH, Lee JS, Lee YJ, Kim KJ, Yoo JJ, Kim HJ. Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis. J Orthop Res. 2006;24:1722–8.

    Article  CAS  PubMed  Google Scholar 

  18. Glueck CJ, Freiberg RA, Boppana S, Wang P. Thrombophilia, hypofibrinolysis, the eNOS T-786C polymorphism, and multifocal osteonecrosis. J Bone Joint Surg Am. 2008;90:2220–9.

    Article  PubMed  Google Scholar 

  19. Hofmann S, Mazieres B. Osteonecrosis: natural course and conservative therapy. Orthopade. 2000;29:403–10.

    CAS  PubMed  Google Scholar 

  20. Mont MA, Zywiel MG, Marker DR, McGrath MS, Delanois RE. The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review. J Bone Joint Surg Am. 2010;92:2165–70.

    Article  PubMed  Google Scholar 

  21. Johnson AJ, Mont MA, Tsao AK, Jones LC. Treatment of femoral head osteonecrosis in the United States: 16-year analysis of the Nationwide inpatient sample. Clin Orthop Relat Res. 2014;472:617–23.

    Article  PubMed  Google Scholar 

  22. Glueck CJ, Freiberg RA, Wissman R, Wang P. Long term anticoagulation (4–16 years) stops progression of idiopathic hip osteonecrosis associated with familial thrombophilia. Adv Orthop. 2015;29:1–7.

    Google Scholar 

  23. Ficat P. Cortisone associated necrosis of bone. In: Hungerford D, editor. Ischemia and necrosis of bone. Baltimore: Williams and Wilkins; 1980. p. 171–6.

    Google Scholar 

  24. 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. Vet Pathol. 2003;40:345–54.

    Article  CAS  PubMed  Google Scholar 

  25. Bjorkman A, Burtscher IM, Svensson PJ, Hillarp A, Besjakov J, Benoni G. Factor V Leiden and the prothrombin 20210A gene mutation and osteonecrosis of the knee. Arch Orthop Trauma Surg. 2005;125:51–5.

    Article  PubMed  Google Scholar 

  26. Balasa VV, Gruppo RA, Glueck CJ, et al. Legg-Calve-Perthes disease and thrombophilia. J Bone Joint Surg Am. 2004;86-A:2642–7.

    Article  PubMed  Google Scholar 

  27. Vosmaer A, Pereira RR, Koenderman JS, Rosendaal FR, Cannegieter SC. Coagulation abnormalities in Legg-Calve-Perthes disease. J Bone Joint Surg Am. 2010;92:121–8.

    Article  CAS  PubMed  Google Scholar 

  28. Glueck CJ, Freiberg RA, Boriel G, et al. The role of the factor V leiden mutation in osteonecrosis of the hip. Clin Appl Thromb Hemost. 2013;19:499–503.

    Article  PubMed  Google Scholar 

  29. Westrich GH, Sculco TP. Prophylaxis against venous thromboembolic disease: costs and controversy. J Bone Joint Surg Am. 2002;84-A:2306–7.

    Article  PubMed  Google Scholar 

  30. Westrich GH, Weksler BB, Glueck CJ, Blumenthal BF, Salvati EA. Correlation of thrombophilia and hypofibrinolysis with pulmonary embolism following total hip arthroplasty: an analysis of genetic factors. J Bone Joint Surg Am. 2002;84-A:2161–7.

    Article  PubMed  Google Scholar 

  31. Westrich GH, Sanchez PM. Prevention and treatment of thromboembolic disease: an overview. Instr Course Lect. 2002;51:471–80.

    PubMed  Google Scholar 

  32. Mont MA, Jones LC, Rajadhyaksha AD, et al. Risk factors for pulmonary emboli after total hip or knee arthroplasty. Clin Orthop Relat Res. 2004;422:154–63.

    Article  Google Scholar 

  33. Glueck CJ, Valdes A, Bowe D, Munsif S, Wang P. The endothelial nitric oxide synthase T-786c mutation, a treatable etiology of Prinzmetal’s angina. Transl Res. 2013;162:64–6.

    Article  CAS  PubMed  Google Scholar 

  34. Glueck CJ, Freiberg RA, Oghene J, Fontaine RN, Wang P. Association between the T-786C eNOS polymorphism and idiopathic osteonecrosis of the head of the femur. J Bone Joint Surg Am. 2007;89:2460–8.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati and from the Division of Orthopaedics’, VA Hospital, Cincinnati, OH, USA

    Charles J. Glueck MD, Ping Wang PhD & Richard A. Freiberg MD

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  1. Charles J. Glueck MD
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  2. Ping Wang PhD
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  3. Richard A. Freiberg MD
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Correspondence to Charles J. Glueck MD .

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Editors and Affiliations

  1. Mayo Clinic, Rochester, Minnesota, USA

    Rafael J. Sierra

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© 2017 Mayo Foundation for Medical Education and Research

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Glueck, C.J., Wang, P., Freiberg, R.A. (2017). Osteonecrosis and Thrombophilia: Pathophysiology, Diagnosis, and Treatment. In: Sierra, R. (eds) Osteonecrosis of the Femoral Head. Springer, Cham. https://doi.org/10.1007/978-3-319-50664-7_1

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  • DOI: https://doi.org/10.1007/978-3-319-50664-7_1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-50662-3

  • Online ISBN: 978-3-319-50664-7

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