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Factor V Leiden and the prothrombin 20210A gene mutation and osteonecrosis of the knee

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Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Introduction

The pathogenesis behind osteonecrosis of the knee is still unknown. Circulatory impairment of the bone secondary to thrombosis in the microcirculation has been suggested as a mechanism. The purpose of this study was to examine the association between osteonecrosis of the knee and abnormalities in the thrombotic pathway in the form of factor V Leiden and the prothrombin 20210A gene mutation.

Materials and methods

Thirty-eight consecutive patients (13 men and 25 women) with osteonecrosis of the knee without a history of knee trauma or surgery to the knee were enrolled in this study. Assays for the detection of factor V Leiden and the prothrombin 20210A gene mutation were performed, and the results were compared with those from 282 healthy volunteers.

Results

Six patients were diagnosed with secondary osteonecrosis, four corticosteroid-induced and two alcohol-induced. In 32 patients, no aetiological factor was found, and these patients were diagnosed with primary osteonecrosis of the knee. Twelve patients had 14 gene mutations, 11 factor V Leiden and 3 prothrombin 20210A gene mutations. Factor V Leiden and the prothrombin 20210A gene mutation occurred significantly (p=0.006) more frequently in patients with osteonecrosis than in a population of 282 healthy volunteers (odds ratio 3.1, 95%CI 1.4–6.6).

Conclusion

The results of this study suggest that coagulation abnormalities in the form of factor V Leiden and the prothrombin 20210A gene mutation might play a role in osteonecrosis of the knee.

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References

  1. Aglietti P, Insall JN, Buzzi R, Deschamps G (1983) Idiopathic osteonecrosis of the knee. Aetiology, prognosis and treatment. J Bone Joint Surg Br 65:588–597

    CAS  PubMed  Google Scholar 

  2. Ahlbäck S, Bauer GCH, Bohne WH (1968) Spontaneous osteonecrosis of the knee. Arthritis Rheum 11:705–733

    PubMed  Google Scholar 

  3. Arnoldi C, Lemperg R, Linderholm H (1975) Intraosseous hypertension and pain in the knee. J Bone Joint Surg Br 57:360–363

    CAS  PubMed  Google Scholar 

  4. Arruda VR, Belangero WD, Ozelo MC, Oliveira GB, Pagnano RG, Volpon JB, Annichino-Bizzacchi JM (1999) Inherited risk factors for thrombophilia among children with Legg-Calvé-Perthes disease. J Pediatr Orthop 19:84–87

    Article  CAS  PubMed  Google Scholar 

  5. Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, Ronde H de, Velden PA van der, Reitsma PH (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67

    Article  CAS  PubMed  Google Scholar 

  6. Ecker ML, Lotke PA (1994) Spontaneous osteonecrosis of the knee. J Am Acad Orthop Surg 2:173–178

    PubMed  Google Scholar 

  7. Emmerich J, Rosendaal FR, Cattaneo M, Margaglione M, De Stefano V, Cumming T, Arruda V, Hillarp A, Reny JL (2001) Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism: pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Thromb Haemost 86:809–816

    CAS  PubMed  Google Scholar 

  8. Glueck CJ, Brandt G, Gruppo R, Crawford A, Roy D, Tracy T, Stroop D, Wang P (1997) Resistance to activated protein C and Legg-Perthes disease. Clin Orthop 338:139–152

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  10. Hayek S, Kenet G, Lubetsky A, Rosenberg N, Gitel S, Wientroub S (1999) Does thrombophilia play an aetiological role in Legg-Calvé-Perthes disease? J Bone Joint Surg Br 81:686–890

    Article  CAS  PubMed  Google Scholar 

  11. Hillarp A, Zöller B, Svensson PJ, Dahlbäck B (1997) The 20210A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis. Thromb Haemost 78:990–992

    CAS  PubMed  Google Scholar 

  12. Hirota Y, Hotokebuchi T, Sugioka Y (1997) Idiopathic osteonecrosis of the femoral head: nationwide epidemiologic studies in Japan. In: Urbaniak JR, Jones JP Jr (eds) Osteonecrosis: etiology, diagnosis and treatment. American Academy of Orthopaedic Surgeons, Rosemont, pp 51–58

  13. Hresko T, McDougall PA, Gorlin JB, Vamvakas EC, Kasser JR, Neufeld EJ (2002) Prospective reevaluation of the association between thrombotic diathesis and Legg-Perthes disease. J Bone Joint Surg Am 84:1613–1618

    Google Scholar 

  14. Jones JP Jr (1992) Intravascular coagulation and osteonecrosis. Clin Orthop 277:41–53

    PubMed  Google Scholar 

  15. Kirkwood BR (1988) Cohort and case-control studies. In: Kirkwood BR (ed) Essentials of medical statistics. Blackwell Scientific Publications, Oxford, pp 177–183

  16. Lieberman JR, Berry DJ, Mont MA, Aaron RK, Callaghan JJ, Rayadhyaksha A, Urbaniak JR (2002) Osteonecrosis of the hip: management in the twenty-first century. J Bone Joint Surg Am 84:834–853

    Google Scholar 

  17. Lotke PA (1997) Tibial osteonecrosis. In: Urbaniak JR, Jones JP Jr (eds) Osteonecrosis: etiology, diagnosis and treatment. American Academy of Orthopaedic Surgeons, Rosemont, pp 425–428

  18. Mankin HJ (1992) Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med 326:1473–1479

    CAS  PubMed  Google Scholar 

  19. Mont MA, Baumgarten KM, Rifai A, Bluemke DA, Jones LC, Hungerford DS (2000) Atraumatic osteonecrosis of the knee. J Bone Joint Surg Am 82:1279–1290

    CAS  PubMed  Google Scholar 

  20. Mont MA, Myers TH, Krackow KA, Hungerford DS (1997) Total knee arthroplasty for corticosteroid associated avascular necrosis of the knee. Clin Orthop 338:124–130

    PubMed  Google Scholar 

  21. Mont MA, Rifai A, Baumgarten KM, Sheldon M, Hungerford DS (2002) Total knee arthroplasty for osteonecrosis. J Bone Joint Surg Am 84:599–603

    Google Scholar 

  22. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996) A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88:3698–3703

    CAS  PubMed  Google Scholar 

  23. Rees DC, Cox M, Clegg JB (1995) World distribution of factor V Leiden. Lancet 346:1133–1134

    Article  CAS  PubMed  Google Scholar 

  24. Robertsson O, Dunbar MJ, Knutsson K, Lidgren L (2000) Past incidence and future demand for knee arthroplasty in Sweden. A report from the Swedish knee arthroplasty register regarding the effect of past and future population changes on the number of athroplasties performed. Acta Orthop Scand 71:376–380

    Article  CAS  PubMed  Google Scholar 

  25. Svensson PJ, Dahlbäck B (1994) Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 330:517–522

    Article  CAS  PubMed  Google Scholar 

  26. Svensson PJ, Zöller B, Mattiasson I, Dahlbäck B (1997) The factor VR506Q mutation causing APC resistance is highly prevalent amongst unselected outpatients with clinically suspected deep venous thrombosis. J Int Med 241:379–385

    Article  CAS  Google Scholar 

  27. Uchio Y, Ochi M, Adachi N, Nishikori T, Kawasaki K (2001) Intraosseous hypertension and venous congestion in osteonecrosis of the knee. Clin Orthop 384:217–223

    Article  PubMed  Google Scholar 

  28. Yamamoto T, Bullough PG (2000) Spontaneous osteonecrosis of the knee: the result of subchondral insufficiency fracture. J. Bone Joint Surg Am 82:858–866

    Article  CAS  PubMed  Google Scholar 

  29. Zöller B, Svensson PJ, He X, Dahlbäck B (1994) Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 94:2521–2524

    PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from Herman Järnhardts Foundation. The above study complies with the current laws of Sweden.

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Authors and Affiliations

  1. Department of Orthopaedics, University Hospital Malmö, 20502, Malmö, Sweden

    Anders Björkman & Göran Benoni

  2. Department of Radiology, University Hospital Lund, 22185, Lund, Sweden

    Isabella M. Burtscher

  3. Department of Coagulation Disorders, University Hospital Malmö, 20502, Malmö, Sweden

    Peter J. Svensson

  4. Department of Clinical Chemistry, University Hospital Malmö, 20502 , Malmö, Sweden

    Andreas Hillarp

  5. Department of Radiology, University Hospital Malmö, 20502, Malmö, Sweden

    Jack Besjakov

  6. Department of Hand Surgery, University Hospital Malmö, 20502, Malmö, Sweden

    Anders Björkman

Authors
  1. Anders Björkman
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  2. Isabella M. Burtscher
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  3. Peter J. Svensson
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  4. Andreas Hillarp
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  5. Jack Besjakov
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  6. Göran Benoni
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Correspondence to Anders Björkman.

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Björkman, A., Burtscher, I.M., Svensson, P.J. et al. Factor V Leiden and the prothrombin 20210A gene mutation and osteonecrosis of the knee. Arch Orthop Trauma Surg 125, 51–55 (2005). https://doi.org/10.1007/s00402-004-0760-8

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  • DOI: https://doi.org/10.1007/s00402-004-0760-8

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