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Das Wachstumsfaktorkomposit aus GDF-5 und mineralisiertem Kollagen verbessert die Ausheilung einer Hüftkopfnekrose

Eine Untersuchung im Tiermodell

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Zusammenfassung

Material und Methode

Im vorliegenden Versuch wurde an 23 Schafen die Wirkung eines bioresorbierbaren Komposits, bestehend aus dem osteotropen Wachstumsfaktor "Growth and Differentiation Factor-5" (GDF-5) in Kombination mit einer mineralisierten Kollagenmatrix (Healos®), im Osteonekrosemodell überprüft.

Ergebnis

Nach 6 und 12 Wochen wurde die Effektivität des Komposits dokumentiert. Hierbei wurde bei den behandelten Tieren eine beschleunigte ossäre Regeneration des Bohrkanals und eine beschleunigte Ausheilung der Nekrose histologisch mit Hilfe der Mikroradiographie und Computertomographie dokumentiert. Histologisch fand sich nach 12 Wochen bei den behandelten Tieren eine weitgehende Ausheilung der Nekrose und des Bohrkanals. Bei den Kontrolltieren war die Nekrose ossär nicht durchbaut und der Bohrkanal partiell mit Bindegewebe aufgefüllt. Wesentliche Nebenwirkungen der Wachstumsfaktoren oder der Matrix wurden nicht dokumentiert.

Fazit

Die Kombination aus minimal-invasiver, dekomprimierender Anbohrung des Nekroseareals in Verbindung mit der Applikation des Wachstumsfaktorkomposits, bestehend aus GDF-5 und einer mineralisierten Kollagenmatrix, zeigte im Tierversuch vielversprechende Ergebnisse. Weitere Studien sind in Vorbereitung. Mittelfristig könnte die Methode die therapeutischen Ergebnisse der frühen Stadien der humanen Hüftkopfnekrose ohne zusätzliche Belastungen der Patienten verbessern.

Abstract

Materials and methods

After creation of necrosis in 23 sheep, the composites were implanted in half of the animals. The animals were sacrificed 6 and 12 weeks after implantation and the femora were harvested. The specimens were investigated by microradiography, computed tomography, and histologically.

Results

The GDF-5 composites were effective in the necrosis model. Osseous regeneration of the necrosis and the drill track were accelerated and enhanced by the composites. In treated animals the necrosis was nearly healed and the drill track was filled with bone after 12 weeks. In the control group the track was partially filled with fibrous tissue and necrotic lesions were still present. Specific side effects of the growth factor or the matrix were not documented. This was documented by histological scoring and CT investigation

Discussion

The application of an absorbable GDF-5 composite in combination with a core decompression procedure may enhance the healing of devitalized bone defects and is a promising approach for further studies.

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Literatur

  1. Arlet J (1992) Nontraumatic avascular necrosis of the femoral head. Past, present, and future. Clin Orthop 277: 12–21

    Google Scholar 

  2. Arlet J, Ficat P (1968) Interêt de la mesure de la pression intramedullaire dans le massif trochantérien chez l'homme en particulaire pour le diagnostic de l'ostéo-necrose fémoro-capitale. Rev Rhumat 35: 250–256

    Google Scholar 

  3. Conzenius MG, Brown TD, Zhang Y, Robinson RA (2002) A new animal model of femoral head necrosis: one that progresses to human- like mechanical failure. J Orthop Res 20/2: 303–309

    Google Scholar 

  4. Fairbank AC, Bhatia D, Jinnah RH, Hungerford DS (1995) Long-term results of core decompression for ischaemic necrosis of the femoral head. J Bone Joint Surg 77-B: 42–49

  5. Gerhart TN, Kirker-Head CA, Vet MA et al. (1993) Healing segmental femoral defects in sheep using recombinant human bone morphogenetic protein. Clin Orthop Res 293: 317–326

    Google Scholar 

  6. Gold EW, Fox OD, Weissfeld S, Curtiss PH (1978) Corticosteroid-induced avascular necrosis: An experimental study on rabbits. Clin Orthop Rel Res 135: 272–280

    Google Scholar 

  7. Heldin, C.H. (1997) TGF-beta signaling from cell membrane to nucleus through SMAD proteins. Nature 390: 465–471

    Google Scholar 

  8. Hofmann S, Kramer J, Leder K, Plenk H Jr, Engel A (1994) Die nichttraumatische Hüftkopfnekrose des Erwachsenen.Teil I: Pathophysiologie, Klinik und therapeutische Möglichkeiten. Radiologe 34/1: 1–10

    Google Scholar 

  9. Hötten G, Neidhardt H, Schneider C, Pohl J (1995) Cloning of a new member of the TGF-beta family: a putative new activin beta C chain. Biochem Biophys Res Commun 206/2: 608–613

    Google Scholar 

  10. Hungerford MW, Mont MA. (2000) Die potentielle Anwendung von Zytokinen und Wachstumsfaktoren bei der Behandlung der Osteonekrose. Orthopäde 29/5:442–448

  11. Kirker-Head CA, Gerhart TN, Schelling SH, Hennig GE, Wang E, Holtrop ME (1995) Long-term healing of bone using recombinant human bone morphogenetic protein 2. Clin Orthop 318: 222–230

    Google Scholar 

  12. Luyten FP (1997) Cartilage-derived morphogenetic protein-1. Int J Biochem Cell Biol 29/11: 1241–1244

    Google Scholar 

  13. Malizos KN; Soucacos PN; Beris AE (1995) Osteonecrosis of the femoral head. Hip salvaging with implantation of a vascularized fibular graft. Clin Orthop 314: 67–75

    Google Scholar 

  14. Manggold, Sergi C, Becker K, Lukoschek M, Simank HG (2002) A new animal model of femoral head necrosis induced by intraosseous injection of ethanol. Lab Anim 36/2: 173–180

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

    Google Scholar 

  16. Mazières B (1994) Bone Morphogenetic Proteins and Bone Necrosis: A Perspective. ARCO News 6: 3–5

    Google Scholar 

  17. Meyers MH (1983) Surgical treatment of osteonecrosis of the femoral head. Instr Course Lect 32: 260–265

    Google Scholar 

  18. Mont MA, Hungerford DS (1995) Non- traumatic avascular osteonecrosis of the femoral head. J Bone Joint Surg 77A: 459–474

    Google Scholar 

  19. Mont MA, Jones LC, Einhorn TA, Hungerford DS, Reddi AH (1998) Osteonecrosis of the femoral head. Potential treatment with growth and differentiation factors. Clin Orthop 355 (Suppl): 314–335

    Google Scholar 

  20. Ninomiya S (1989) An epidemiological survey of idiopathic avascular necrosis of the femoral head in Japan. Annual Report of Japanese Investigation Committee for Intractable Diseases. Tokyo, Ministry of Health and Welfare, 26

  21. Schneider W, Breitenseher M, Engel A, Knahr K, Plenk H, Hofmann S (2000) Der Stellenwert der Bohrung in der Behandlung der Hüftkopfnekrose. Orthopäde 29: 420–429

    Google Scholar 

  22. Scully SP, Rizk WAS, Seaber AV, Urbaniak JR (1995) Augmentation of subchondral bone formation in AVN with rhBMP-2. Trans Orthop Res Soc 20: 495

    Google Scholar 

  23. Seeherman HJ, Blake CA, Luppen CA, Bouxsein ML, Li J, Wozney JM (2000) RhBMP-2 stimulates remodelling and bone formation in a nonhuman primate core defect model. Transactions 25: 1042

    Google Scholar 

  24. Simank HG, Brocai DR, Brill C, Lukoschek M (2001) Comparison of results of core decompression and intertrochanteric osteotomy for nontraumatic osteonecrosis of the femoral head using Cox regression and survivorship analysis. J Arthroplasty 16: 790–794

    Google Scholar 

  25. Spiro RC, Liu L, Heidaran MA, Thompson AY, Ng CK, Pohl J, Poser JW (2000) Inductive activity of recombinant human growth and differentiation factor-5. Biochem Soc Trans 28/4: 362–368

    Google Scholar 

  26. Spiro RC, Thompson AY, Poser JW (2001) Spinal fusion with recombinant human growth and differentiation factor-5 combined with a mineralized collagen matrix. Anat Rec 263/4: 388–395

    Google Scholar 

  27. Tay BK, Le AX, Heilman M, Lotz J, Bradford DS (1998) Use of a collagen-hydroxyapatite matrix in spinal fusion. A rabbit model. Spine 23/21: 2276–2281

    Google Scholar 

  28. Urist MR (1965) Bone: Formation by autoinduction. Science 150: 893–899

    Google Scholar 

  29. Yamashita H, Shimuzu A, Kato M, Nishito H et al. (1997) Growth/differentiation factor 5 produces angiogenesis in vivo. Exp Cell Res 235: 218–226

    Google Scholar 

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Authors and Affiliations

  1. Orthopädische Universitätsklinik Heidelberg

    H.-G. Simank, F. Herold & M. Schneider

  2. Diagnostische Radiologie der Universität Heidelberg

    U. Maedler

  3. Firma Biopharm, Heidelberg

    R. Ries

  4. Department of Pathology, St. Michael's University Hospital, Bristol, United Kingdom

    C. Sergi

  5. Orthopädische Universitätsklinik Heidelberg, Schlierbacher Landstraße 200a, 69118, Heidelberg

    H.-G. Simank

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  1. H.-G. Simank
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  2. F. Herold
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  3. M. Schneider
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  4. U. Maedler
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  5. R. Ries
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  6. C. Sergi
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Correspondence to H.-G. Simank.

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Simank, HG., Herold, F., Schneider, M. et al. Das Wachstumsfaktorkomposit aus GDF-5 und mineralisiertem Kollagen verbessert die Ausheilung einer Hüftkopfnekrose. Orthopäde 33, 68–75 (2004). https://doi.org/10.1007/s00132-003-0541-z

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