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Effects of Fondaparinux Compared with Dalteparin, Enoxaparin and Unfractionated Heparin on Human Osteoblasts

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Abstract

The objective of the this study was to examine the effects of fondaparinux, a synthetic anticoagulant substance similar to heparin, on osteoblasts compared with previously used heparins. Its effects have been shown in clinical trials to be highly effective in thromboembolism prophylaxis. Unfractionated heparin (UFH), dalteparin, enoxaparin and fondaparinux were added to osteoblast cultures in the therapeutic range and two decimal powers above and below it in each case. The results showed that the mitochondrial activity and protein synthesis of osteoblasts treated with fondaparinux were significantly higher than in the other groups. Similar effects could be demonstrated for the matrix collagen type II content and calcification. In contrast enoxaparin, dalteparin and UFH lead to a significant decrease of matrix collagen type II content and calcification in concentrations equal or higher than the therapeutic one. No inhibitory in-vitro effects of fondaparinux on human osteoblasts could be demonstrated within the concentration range investigated (0.01 – 100 µg/ml). We conclude that fondaparinux can be used to avoid the heparin-related negative influence on osteoblast-dependent fracture healing and endoprosthetic implant integration.

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References

  1. JR Leclerc WH Geerts L Desjardins F Jobin F Laroche F Delorme S Haviernick S Atkinson J Bourgouin (1992) ArticleTitlePrevention of deep vein thrombosis after major knee surgery–a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Haemost 67 417–423 Occurrence Handle1:STN:280:By2A3snhs1E%3D Occurrence Handle1321509

    CAS  PubMed  Google Scholar 

  2. PA Moskovitz SS Ellenberg HL Feffer PI Kenmore RJ Neviaser BE Rubin VM Varma (1978) ArticleTitleLow-dose heparin for prevention of venous thromboembolism in total hip arthroplasty and surgical repair of hip fractures. J Bone Joint Surg Am 60 1065–1070 Occurrence Handle1:STN:280:CSaD28joslU%3D Occurrence Handle363722

    CAS  PubMed  Google Scholar 

  3. CW Francis VD Pellegrini Jr S Totterman AD Boyd et al. (1997) ArticleTitlePrevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin. J Bone Joint Surg Am 79 1365–1372 Occurrence Handle1:STN:280:ByiH2MfgsFE%3D Occurrence Handle9314399

    CAS  PubMed  Google Scholar 

  4. CW Colwell Jr TE Spiro (1995) ArticleTitleEfficacy and safety of enoxaparin to prevent deep vein thrombosis after hip arthroplasty. Clin Orthop 215–222 Occurrence Handle7671481

    PubMed  Google Scholar 

  5. BI Eriksson KA Bauer MR Lassen AG Turpie (2001) ArticleTitleFondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med 345 1298–1304 Occurrence Handle10.1056/NEJMoa011100 Occurrence Handle1:CAS:528:DC%2BD3MXnvV2ltr0%3D Occurrence Handle11794148

    Article  CAS  PubMed  Google Scholar 

  6. N Akkas YN Yeni B Turan E Delilbasi U Gunel (1997) ArticleTitleEffect of medication on biomechanical properties of rabbit bones: heparin-induced osteoporosis. Clin Rheumatol 16 585–595 Occurrence Handle1:STN:280:DyaK1c7hsFGntA%3D%3D Occurrence Handle9456011

    CAS  PubMed  Google Scholar 

  7. LA Barbour SD Kick JF Steiner ME LoVerde LN Heddleston JL Lear AE Baron PL Barton (1994) ArticleTitleA prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 170 862–869 Occurrence Handle1:STN:280:ByuC1cbmsVc%3D Occurrence Handle8141217

    CAS  PubMed  Google Scholar 

  8. M Bhandari J Hirsh JI Weitz E Young TJ Venner SG Shaughnessy (1998) ArticleTitleThe effects of standard and low molecular weight heparin on bone nodule formation in vitro. Thromb Haemost 80 413–417 Occurrence Handle1:CAS:528:DyaK1cXmtFCls7w%3D Occurrence Handle9759620

    CAS  PubMed  Google Scholar 

  9. DJ Mazanec JM Grisanti (1989) ArticleTitleDrug-induced osteoporosis. Cleve Clin J Med 56 297–303 Occurrence Handle1:STN:280:BiaA3cvjvF0%3D Occurrence Handle2663221

    CAS  PubMed  Google Scholar 

  10. JM Muir M Andrew J Hirsh JI Weitz E Young P Deschamps SG Shaughnessy (1996) ArticleTitleHistomorphometric analysis of the effects of standard heparin on trabecular bone in vivo. Blood 88 1314–1320 Occurrence Handle1:CAS:528:DyaK28XkvF2js7w%3D Occurrence Handle8695849

    CAS  PubMed  Google Scholar 

  11. S Deo CL Gibbons M Emerton AH Simpson (1995) ArticleTitleTotal hip replacement in renal transplant patients. J Bone Joint Surg Br 77 299–302 Occurrence Handle1:STN:280:ByqB387kslA%3D Occurrence Handle7706352

    CAS  PubMed  Google Scholar 

  12. VJ Devlin TA Einhorn SL Gordon EV Alvarez KM Butt (1988) ArticleTitleTotal hip arthroplasty after renal transplantation. Long-term follow-up study and assessment of metabolic bone status. J Arthroplasty 3 205–213

    Google Scholar 

  13. S Kobayashi NS Eftekhar K Terayama (1994) ArticleTitlePredisposing factors in fixation failure of femoral prostheses following primary Charnley low friction arthroplasty. A 10- to 20-year followup study. Clin Orthop 73–83

    Google Scholar 

  14. F Stinchfield B Sankaran R Samilson (1955) ArticleTitleThe effect of anticoagulant therapy on bone repair. J Bone Joint Surg Br 28-A 270–282

    Google Scholar 

  15. NW Roehm GH Rodgers SM Hatfield AL Glasebrook (1991) ArticleTitleAn improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. J Immunol Methods 142 257–265 Occurrence Handle1:STN:280:By2D3MzhvFU%3D Occurrence Handle1919029

    CAS  PubMed  Google Scholar 

  16. DA Scudiero RH Shoemaker KD Paull et al. (1988) ArticleTitleEvaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 48 4827–4833 Occurrence Handle1:CAS:528:DyaL1cXls1arsrk%3D Occurrence Handle3409223

    CAS  PubMed  Google Scholar 

  17. SG Shaughnessy J Hirsh M Bhandari JM Muir E Young JI Weitz (1999) ArticleTitleA histomorphometric evaluation of heparin-induced bone loss after discontinuation of heparin treatment in rats. Blood 93 1231–1236 Occurrence Handle1:CAS:528:DyaK1MXht1Cjtbs%3D Occurrence Handle9949165

    CAS  PubMed  Google Scholar 

  18. WJ Murray VS Lindo VV Kakkar E Melissari (1995) ArticleTitleLong-term administration of heparin and heparin fractions and osteoporosis in experimental animals. Blood Coagul Fibrinolysis 6 113–118 Occurrence Handle1:CAS:528:DyaK2MXlvVKqsL4%3D Occurrence Handle7605875

    CAS  PubMed  Google Scholar 

  19. SG Shaughnessy E Young P Deschamps J Hirsh (1995) ArticleTitleThe effects of low molecular weight and standard heparin on calcium loss from fetal rat calvaria. Blood 86 1368–1373 Occurrence Handle1:CAS:528:DyaK2MXnsVClsbk%3D Occurrence Handle7632944

    CAS  PubMed  Google Scholar 

  20. MK von der G Conrad (1979) ArticleTitleCartilage cell differentiation: review. Clin Orthop 185–205

    Google Scholar 

  21. H Denissen J de Blieck H Verhey C Klein A Van Lingen (1996) ArticleTitleDual-energy X-ray absorptiometry for histologic bone sections. J Bone Miner Res 11 638–644 Occurrence Handle1:STN:280:ByiD3M3mslE%3D Occurrence Handle9157778

    CAS  PubMed  Google Scholar 

  22. AC Ruifrok DA Johnston (2001) ArticleTitleQuantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol 23 291–299 Occurrence Handle1:STN:280:DC%2BD3MvovVymsA%3D%3D Occurrence Handle11531144

    CAS  PubMed  Google Scholar 

  23. JW Squires LW Pinch (1979) ArticleTitleHeparin-induced spinal fractures. JAMA 241 2417–2418 Occurrence Handle10.1001/jama.241.22.2417 Occurrence Handle1:STN:280:CSaC2srlvF0%3D Occurrence Handle439319

    Article  CAS  PubMed  Google Scholar 

  24. C Rasmussen J Wadt B Jacobsen (1994) ArticleTitleThromboembolic prophylaxis with low molecular weight heparin during pregnancy. Int J Gynaecol Obstet 47 121–125 Occurrence Handle1:STN:280:ByqC2crotVY%3D Occurrence Handle7843480

    CAS  PubMed  Google Scholar 

  25. DF Volles CJ Ancell KA Michael DM Mullins JE Humphries (1998) ArticleTitleEstablishing an institution-specific therapeutic range for heparin. Am J Health Syst Pharm 55 2002–2006 Occurrence Handle1:CAS:528:DyaK1cXmslKksLg%3D Occurrence Handle9784787

    CAS  PubMed  Google Scholar 

  26. S Ahmad WP Jeske Q Ma JM Walenga J Fareed (2001) ArticleTitleInhibition of tissue factor-activated platelets by low-molecular-weight heparins and glycoprotein IIb/IIIa receptor antagonist. Thromb Res 102 143–151 Occurrence Handle10.1016/S0049-3848(01)00225-0 Occurrence Handle1:CAS:528:DC%2BD3MXivFart7Y%3D Occurrence Handle11323025

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedics, Charité University Hospital, Schumannstr. 20-21, 10117 Berlin, Germany

    G. Matziolis, C. Perka, A. Disch & H. Zippel

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  1. G. Matziolis
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  2. C. Perka
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  3. A. Disch
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  4. H. Zippel
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Correspondence to G. Matziolis.

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Matziolis, G., Perka, C., Disch, A. et al. Effects of Fondaparinux Compared with Dalteparin, Enoxaparin and Unfractionated Heparin on Human Osteoblasts. Calcif Tissue Int 73, 370–379 (2003). https://doi.org/10.1007/s00223-002-2091-5

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  • DOI: https://doi.org/10.1007/s00223-002-2091-5

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