Skip to main content
SpringerLink
Log in

Treatment of Osteonecrosis of the Hip and Knee with Enoxaparin

  • Chapter
  • First Online:
Osteonecrosis

Abstract

In a prospective study, we hypothesized that a 3-month course of enoxaparin would prevent progression of Ficat stages I–II primary osteonecrosis (ON) of the hip(s) associated with thrombophilia-hypofibrinolysis, having previously shown that despite enoxaparin, hips staged as Ficat III or IV routinely progressed to total hip replacement (THR) as did hips in patients with ON secondary to corticosteroids, alcohol, etc. After 3 months on enoxaparin, 20 patients (30 hips) with ≥ 1 thrombophilia-hypofibrinolysis and Ficat stages I–II primary ON of ≥ 1 hip were followed for 4–7 years. Maintenance of Ficat stages I–II versus progression to stages III–IV or THR over a follow-up period of 4–7 years was the current study’s endpoint. The first 16 patients (25 hips) received enoxaparin (60 mg/day) for 3 months. The next 4 patients (5 hips) received enoxaparin 1.5 mg/kg/day for 3 months. Two of these 4 patients were subsequently maintained on enoxaparin and then Xarelto 10 mg/day for 6 years, and Warfarin (INR 3–3.5) for 13 years, respectively. Based on intent to treat, at 4-year follow-up, 22 of the original 30 hips (73 %) remained unchanged (Ficat stages I or II), as did 16 of 30 hips (53 %) at 7 years. The two patients with chronic anticoagulation had no change from pretreatment Ficat I–II ON of ≥ 1 hip at 6 and 13 years follow-up. Compared with untreated historical controls (approximately 20 % 2-year hip survival), 4-year survival of 73 % of hips, based on intent to treat, suggests that the original 12 week enoxaparin treatment produces lasting benefit in primary ON in patients with heritable thrombophilia-hypofibrinolysis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Glueck CJ, Goldenberg N, Budhani S, Lotner D, Abuchaibe C, Gowda M, et al. Thrombotic events after starting exogenous testosterone in men with previously undiagnosed familial thrombophilia. Transl Res. 2011;158(4):225–34. doi:S1931-5244(11)00191-5 [pii] 10.1016/j.trsl.2011.06.003.

  2. 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(1):51–5. doi:10.1007/s00402-004-0760-8.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. 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(10):2220–9. doi:90/10/2220 [pii] 10.2106/JBJS.G.00616.

  5. Glueck CJ, Freiberg RA, Wang P. Heritable thrombophilia-hypofibrinolysis and osteonecrosis of the femoral head. Clin Orthop Relat Res. 2008;466(5):1034–40. doi:10.1007/s11999-008-0148-0.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Pierre-Jacques H, Glueck CJ, Mont MA, Hungerford DS. Familial heterozygous protein-S deficiency in a patient who had multifocal osteonecrosis. A case report. J Bone Joint Surg Am. 1997;79(7):1079–84.

    CAS  PubMed  Google Scholar 

  7. Glueck CJ, Freiberg RA, Wang P. Detecting thrombophilia, hypofibrinolysis, and reduced nitric oxide production in osteonecrosis. Semin Arthroplasty. 2007;18:184–91.

    Article  Google Scholar 

  8. Zalavras C, Dailiana Z, Elisaf M, Bairaktari E, Vlachogiannopoulos P, Katsaraki A, et al. Potential aetiological factors concerning the development of osteonecrosis of the femoral head. Eur J Clin Invest. 2000;30(3):215–21.

    Article  CAS  PubMed  Google Scholar 

  9. Jones JJ. Activating intravascular coagulation and causing nontraumatic osteonecrosis. In: Urbaniak JR, Jones Jr JP, editors. Osteonecrosis: etiology, diagnosis, and treatment. Rosemont: American Academy of Orthopedic Surgeons; 1997. p. 89–97.

    Google Scholar 

  10. Jones LC, Mont MA, Le TB, Petri M, Hungerford DS, Wang P, et al. Procoagulants and osteonecrosis. J Rheumatol. 2003;30(4):783–91.

    CAS  PubMed  Google Scholar 

  11. Koo KH, Kim R, Cho SH, Song HR, Lee G, Ko GH. Angiography, scintigraphy, intraosseous pressure, and histologic findings in high-risk osteonecrotic femoral heads with negative magnetic resonance images. Clin Orthop. 1994;308:127–38.

    PubMed  Google Scholar 

  12. Korompilias AV, Ortel TL, Urbaniak JR. Coagulation abnormalities in patients with hip osteonecrosis. Orthop Clin North Am. 2004;35(3):265–71. vii.

    Article  PubMed  Google Scholar 

  13. 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  PubMed  Google Scholar 

  14. Nilsson IM, Krook H, Sternby NH, Soderberg E, Soderstrom N. Severe thrombotic disease in a young man with bone marrow and skeletal changes and with a high content of an inhibitor in the fibrinolytic system. Acta Med Scand. 1961;169:323–37.

    Article  CAS  PubMed  Google Scholar 

  15. Balasa VV, Gruppo RA, Glueck CJ, Wang P, Roy DR, Wall EJ, et al. Legg-Calve-Perthes disease and thrombophilia. J Bone Joint Surg Am. 2004;86-A(12):2642–7.

    PubMed  Google Scholar 

  16. Vosmaer A, Pereira RR, Koenderman JS, Rosendaal FR, Cannegieter SC. Coagulation abnormalities in Legg-Calve-Perthes disease. J Bone Joint Surg Am. 2010;92(1):121–8. doi:92/1/121 [pii] 10.2106/JBJS.I.00157.

  17. 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  PubMed  Google Scholar 

  18. Lindahl TL, Lundahl TH, Nilsson L, Andersson CA. APC-resistance is a risk factor for postoperative thromboembolism in elective replacement of the hip or knee–a prospective study. Thromb Haemost. 1999;81(1):18–21. doi:99010018 [pii].

    Google Scholar 

  19. Szucs G, Ajzner E, Muszbek L, Simon T, Szepesi K, Fulesdi B. Assessment of thrombotic risk factors predisposing to thromboembolic complications in prosthetic orthopedic surgery. J Orthop Sci. 2009;14(5):484–90. doi:10.1007/s00776-009-1368-1.

    Article  PubMed  Google Scholar 

  20. Wahlander K, Larson G, Lindahl TL, Andersson C, Frison L, Gustafsson D, et al. Factor V Leiden (G1691A) and prothrombin gene G20210A mutations as potential risk factors for venous thromboembolism after total hip or total knee replacement surgery. Thromb Haemost. 2002;87(4):580–5.

    CAS  PubMed  Google Scholar 

  21. Mont MA, Jones LC, Rajadhyaksha AD, Shuler MS, Hungerford DS, Sieve-Smith L, et al. Risk factors for pulmonary emboli after total hip or knee arthroplasty. Clin Orthop Relat Res. 2004;(422):154–63. doi:00003086-200405000-00026 [pii].

    Google Scholar 

  22. Salvati EA, Della Valle AG, Westrich GH, Rana AJ, Specht L, Weksler BB, et al. The John Charnley Award: heritable thrombophilia and development of thromboembolic disease after total hip arthroplasty. Clin Orthop Relat Res. 2005;441:40–55. doi:00003086-200512000-00010 [pii].

    Google Scholar 

  23. 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(4):345–54.

    Article  CAS  PubMed  Google Scholar 

  24. Laroche M. Intraosseous circulation from physiology to disease. Joint Bone Spine. 2002;69(3):262–9.

    Article  PubMed  Google Scholar 

  25. Liu SL, Ho TC. The role of venous hypertension in the pathogenesis of Legg-Perthes disease. A clinical and experimental study. J Bone Joint Surg Am. 1991;73(2):194–200.

    CAS  PubMed  Google Scholar 

  26. Norman D, Miller Y, Sabo E, Misselevich I, Peskin B, Zinman C, et al. The effects of enoxaparin on the reparative processes in experimental osteonecrosis of the femoral head of the rat. Apmis. 2002;110(3):221–8.

    Article  CAS  PubMed  Google Scholar 

  27. Norman D, Reis D, Zinman C, Misselevich I, Boss JH. Vascular deprivation-induced necrosis of the femoral head of the rat. An experimental model of avascular osteonecrosis in the skeletally immature individual or Legg-Perthes disease. Int J Exp Pathol. 1998;79(3):173–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Lafforgue P. Pathophysiology and natural history of avascular necrosis of bone. Joint Bone Spine. 2006;73:500–7.

    Article  CAS  PubMed  Google Scholar 

  29. 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 

  30. Glueck CJ, Freiberg RA, Fontaine RN, Sieve-Smith L, Wang P. Anticoagulant therapy for osteonecrosis associated with heritable hypofibrinolysis and thrombophilia. Expert Opin Investig Drugs. 2001;10(7):1309–16.

    Article  CAS  PubMed  Google Scholar 

  31. Glueck CJ, Freiberg RA, Wang P. Role of thrombosis in osteonecrosis. Curr Hematol Rep. 2003;2(5):417–22.

    CAS  PubMed  Google Scholar 

  32. Jones JP. Risk factors potentially activating intravascular coagulation and causing nontraumatic osteonecrosis. In: Urbaniak JR, Jones Jr JP, editors. Osteonecrosis: etiology, diagnosis, and treatment. Rosemont: American Academy of Orthopedic Surgeons; 1997. p. 89–97.

    Google Scholar 

  33. Zalavras CG, Vartholomatos G, Dokou E, Malizos KN. Genetic background of osteonecrosis: associated with thrombophilic mutations? Clin Orthop. 2004;422:251–5.

    Article  PubMed  Google Scholar 

  34. CotBTS R. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. Research Committee of the British Thoracic Society. Lancet. 1992;340(8824):873–6.

    Google Scholar 

  35. Arlet J, Ficat P. Diagnosis of primary femur head osteonecrosis at stage 1 (preradiologic stage). Rev Chir Orthop Reparatrice Appar Mot. 1968;54(7):637–48.

    CAS  PubMed  Google Scholar 

  36. Hofmann S, Mazieres B. Osteonecrosis: natural course and conservative therapy. Orthopade. 2000;29(5):403–10.

    CAS  PubMed  Google Scholar 

  37. Koo KH, Kim R, Ko GH, Song HR, Jeong ST, Cho SH. Preventing collapse in early osteonecrosis of the femoral head. A randomised clinical trial of core decompression. J Bone Joint Surg Br. 1995;77(6):870–4.

    CAS  PubMed  Google Scholar 

  38. Stulberg BN, Davis AW, Bauer TW, Levine M, Easley K. Osteonecrosis of the femoral head. A prospective randomized treatment protocol. Clin Orthop. 1991;268:140–51.

    PubMed  Google Scholar 

  39. Satku K, Kumar VP, Chong SM, Thambyah A. The natural history of spontaneous osteonecrosis of the medial tibial plateau. J Bone Joint Surg Br. 2003;85(7):983–8.

    Article  CAS  PubMed  Google Scholar 

  40. Coogan PG, Urbaniak JR. Multicenter experience with free vascularized fibular grafts for osteonecrosis of the femoral head. In: Urbaniak JR, Jones Jr JP, editors. Osteonecrosis: etiology, diagnosis, and treatment. Rosemont: American Academy of Orthopedic Surgeons; 1997. p. 327–52.

    Google Scholar 

  41. Garino JP, Steinberg ME. Total hip arthroplasty in patients with avascular necrosis of the femoral head: a 2- to 10-year follow-up. Clin Orthop. 1997;334:108–15.

    PubMed  Google Scholar 

  42. Ritter MA, Helphinstine J, Keating EM, Faris PM, Meding JB. Total hip arthroplasty in patients with osteonecrosis. The effect of cement techniques. Clin Orthop. 1997;338:94–9.

    Article  PubMed  Google Scholar 

  43. Robinson Jr HJ. Success of core decompression in the management of early stages of avascular necrosis: a four year prospective study. In: Proceedings of the American Academy of Orthopaedic Surgeons 59th annual meeting. Washington, DC: American Academy of Orthopedic Surgeons; 1992. p. 177.

    Google Scholar 

  44. Steinberg M, Larcom PG, Stafford BB. Treatment of osteonecrosis of the femoral head by core decompression, bone grafting, and electrical stimulation. In: Urbaniak JR, Jones Jr JP, editors. Osteonecroiss: etiology, diagnosis, and treatment. Rosemont: American Academy of Orthopedic Surgeons; 1997. p. 293–9.

    Google Scholar 

  45. Stulberg BN, Singer R, Goldner J, Stulberg J. Uncemented total hip arthroplasty in osteonecrosis: a 2- to 10-year evaluation. Clin Orthop. 1997;334:116–23.

    PubMed  Google Scholar 

  46. Yasunaga Y, Ikuta Y, Omoto O, Shigenobu T, Itoh K, Fukuoka H, et al. Transtrochanteric rotational osteotomy for osteonecrosis of the femoral head with preoperative superselective angiography. Arch Orthop Trauma Surg. 2000;120(7–8):437–40.

    Article  CAS  PubMed  Google Scholar 

  47. Lieberman JR. Core decompression for osteonecrosis of the hip. Clin Orthop. 2004;418:29–33.

    Article  PubMed  Google Scholar 

  48. Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME. Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum. 2002;32(2):94–124.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study followed a protocol approved by the Jewish Hospital IRB, with written informed consent.

The study was supported by the Lipoprotein Research Fund and by the Medical Research Council of the Jewish Hospital

Author information

Authors and Affiliations

  1. The Cholesterol Center, Jewish Hospital of Cincinnati, ABC Building, 3200 Burnet Ave, Cincinnati, OH, 45229, USA

    Charles J. Glueck & Ping Wang

  2. Department of Surgery, Orthopedic Surgery Service VA Hospital, Cincinnati, OH, USA

    Richard A. Freiberg

Authors
  1. Charles J. Glueck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard A. Freiberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles J. Glueck .

Editor information

Editors and Affiliations

  1. Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Kyonggi-do, Korea, Republic of (South Korea)

    Kyung-Hoi Koo

  2. Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, Maryland, USA

    Michael A. Mont

  3. Department of Orthopaedic Surgery, Department of Orthopaedic Surgery, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Lynne C. Jones

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Glueck, C.J., Freiberg, R.A., Wang, P. (2014). Treatment of Osteonecrosis of the Hip and Knee with Enoxaparin. In: Koo, KH., Mont, M., Jones, L. (eds) Osteonecrosis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-35767-1_32

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-35767-1_32

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-35766-4

  • Online ISBN: 978-3-642-35767-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation