Skip to main content

Advertisement

SpringerLink
Log in

Clinical application of BMP 7 in long bone non-unions

  • Trauma Surgery
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Background

Non-unions of long bone fractures are a therapeutic and economic problem of increasing frequency. Aside from conservative treatment options such as ultrasound, impulse waves, and casts, the basic surgical options are autogenous cancellous bone grafting, rod dynamization, reamed nailing, plate fixation, and bone transport techniques. If these methods fail to work, there is a need for alternative treatment options.

Methods

Since May 2001, treatment with recombinant human bone morphogenic protein 7 (BMP 7 or osteogenic protein 1) in combination with a type-one collagen carrier has been the subject of increasing interest. BMP 7 induces the formation of new bone by stem cell differentiation, thereby initiating the reaction cascade of osteogenesis. Non-unions over 9 months and unsuccessful bone grafting constitute the indication for this treatment.

Results

We report our experience with 54 patients who had atrophic non-union of long bone fractures. Between May 2002 and May 2006, 57 units of BMP 7 were used. The localization of the non-unions included 21 in the femur, 26 in the tibia, 3 in the humerus and 7 in the forearm. In 36 cases, BMP 7 was used in combination with osteosynthesis revision and bone grafting; in 9 additional patients, BMP 7 was used with bone grafting alone. In 12 patients, BMP 7 was applied as a single procedure without any bone grafting or any change in osteosynthesis.

Conclusions

There were no perioperative or postoperative complications. Follow-up was obtained for a minimum of 6 months. 47 of the 57 (82%) implantations were successful, with bony healing confirmed by clinical and radiological evaluation. In summary, our results support BMP 7 as an additional innovative therapy for long bone non-unions.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Allan HL, Wase A, Bear WT (1980) Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat. Acta Orthop Scand 51:595–600

    Article  Google Scholar 

  2. Augat P, Merk J, Ingnatius A et al (1996) Early, full weight-bearing with flexible fixation delays fracture healing. Clin Orthop Relat Res 328:194–202

    Article  PubMed  Google Scholar 

  3. Bergmann A, Schwarz BHM (1989) Cause, prognosis and therapy of tibial pseudarthroses. Aktuelle Traumatol 19:205–208

    CAS  PubMed  Google Scholar 

  4. Brinker MR, Bailey DE Jr (1997) Fracture healing in tibia fractures with an associated vascular injury. J Trauma 42:11–19

    Article  CAS  PubMed  Google Scholar 

  5. Castillo RC, Bosse MJ, MacKenzie EJ, Patterson BM (2005) Impact of smoking on fracture healing and risk of complications in limb-threatening open tibia fractures. J Orthop Trauma 19:151–157

    Article  PubMed  Google Scholar 

  6. Chapman MW, Finkemeier CG (1999) Treatment of supracondylar nonunions of the femur with plate fixation and bone graft. J Bone Joint Surgery Am 81:1217–1228

    CAS  Google Scholar 

  7. Claes L, Augat P, Suger G, Wilke HJ (1997) Influence of size and stability of the osteotomy gap on success of fracture healing. J Orthop Res 15:577–584

    Article  CAS  PubMed  Google Scholar 

  8. Cook SD, Ryaby JB, McCabe J et al (1997) Acceleration of tibial and distal radius fracture healing in patients who smokes. Clin Orthop Releat Res 337:198–207

    Article  Google Scholar 

  9. Cruess RL, Sakai T (1972) The effect of cortisone upon synthesis rates of some components of rat bone matrix. Clin Orthop Relat Res 86:253–259

    Article  CAS  PubMed  Google Scholar 

  10. Daftari TK, Whitesides TE, Heller JG et al (1994) Nicotine on the revascularization of bone graft: an experimental study in rabbits. Spine 19:904–911

    Article  CAS  PubMed  Google Scholar 

  11. Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res 355S:7–21

    Article  Google Scholar 

  12. Einhorn TA, Bonnarens F, Burnstein AH (1986) The contributions of dietary protein and mineral to the healing of experimental fractures. An biomechanical study. J Bone Joint Surg A 68:1389–1395

    CAS  Google Scholar 

  13. Esterhai JL, Brighton CT, Heppenstall RB et al (1986) Nonunion of the humerus: clinical, roentgenographic, scintigraphic and response characteristics to treatment with constant direct current simulation of osteogenesis. Clin Orthop Releat Res 211:228–234

    Google Scholar 

  14. Foster RJ, Dixon GL, Bach AW et al (1985) Internal fixation of fractures an nonunions of the humeral shaft. J Bone Joint Surg A 67:857–864

    CAS  Google Scholar 

  15. Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF, Zych GA, Calhoun JH, LaForte AJ, Yin S (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am A 83(Suppl 1):S151–S158

    Google Scholar 

  16. Geesink RG, Hoefnagels NH, Bulstra SK (1999) Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect. J Bone Joint Surg Br 81:710–718

    Article  CAS  PubMed  Google Scholar 

  17. Gelberman RH, Menon J (1980) The vascularity of the scaphoid bone. J Hand Surg 5:508–513

    CAS  Google Scholar 

  18. Giannoudis PV, Tzioupis C (2005) Clinical applications of BMP-7. The UK perspective. Injury 36S:47–50

    Article  Google Scholar 

  19. Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R, Aro H, Atar D, Bishay M, Borner MG, Chiron P, Choong P, Cinats J, Courtenay B, Feibel R, Geulette B, Gravel C, Haas N, Raschke M, Hammacher E, van der Velde D, Hardy P, Holt M, Josten C, Ketterl RL, Lindeque B, Lob G, Mathevon H, McCoy G, Marsh D, Miller R, Munting E, Oevre S, Nordsletten L, Patel A, Pohl A, Rennie W, Reynders P, Rommens PM, Rondia J, Rossouw WC, Daneel PJ, Ruff S, Ruter A, Santavirta S, Schildhauer TA, Gekle C, Schnettler R, Segal D, Seiler H, Snowdowne RB, Stapert J, Taglang G, Verdonk R, Vogels L, Weckbach A, Wentzensen A, Wisniewski T (2002) Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am A 84:2123–2134

    Google Scholar 

  20. Hayda RA, Brighton CT, Esterhai JL (1998) Pathophysiology of delayed healing. Clin Orthop Relat Res 355S:31–40

    Article  Google Scholar 

  21. Healy WL, White GM, Mick CA et al (1987) Nonunion of the humeral shaft. Clin Orthop Relat Res 219:206–213

    PubMed  Google Scholar 

  22. Henle P, Zimmermann G, Weiss S (2005) Matrix metalloproteinases and failed fracture healing. Bone 37:791–798

    Article  CAS  PubMed  Google Scholar 

  23. Hukkanen M, Konttinen YT, Santavirta A et al (1993) Rapid proliferation of calcitonin gene-related peptide-immunoreactive nerves during healing of rat tibial fracture suggests neural involvement in bone growth and remodelling. Neuroscience 54:969–979

    Article  CAS  PubMed  Google Scholar 

  24. Kwiatkowski TC, Hanley JEN, Ramp WK (1996) Cigarette smoking and its orthopaedic consequences. Am J Orthop 25:590–597

    CAS  PubMed  Google Scholar 

  25. Larson RL, Sukkivan CR, Janes JM (1961) Trauma surgery and the circulation of the talus: what are the risks of avascular necrosis? J Trauma 1:13–21

    Article  Google Scholar 

  26. Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. J Bone Joint Surg Am 84-A:1032–1044

    PubMed  Google Scholar 

  27. Macey LR, Kana SM, Jingushi S et al (1989) Defects of early fracture healing in experimental diabetes. J Bone Joint Surg A 71:722–733

    CAS  Google Scholar 

  28. McKee MD (2005) Recombinant human bone morphogenic protein-7: applications for clinical trauma. J Orthop Trauma 19:S26–S28

    Article  PubMed  Google Scholar 

  29. Nelson GE, Kelly PJ, Peterson F et al (1960) Blood supply of the human tibia. J Bone Joint Surg A 42:625–635

    Google Scholar 

  30. Nunamaker DM (1998) Experimental models of fracture repair. Clin Orthop Releat Res 355S:56–65

    Article  Google Scholar 

  31. Oestern HJ (1997) Die gesundheitspolitische Bedeutung der Unfallchirurgie in Deutschland und Ihre Auswirkung auf Gesellschaft und Wirtschaft. In: Oestern HJ, Probst J (eds) Unfallchirurgie in Deutschland. Springer, Heidelberg, pp 63–79

    Google Scholar 

  32. Reddi AH (1998) Initiation of fracture repair by bone morphogenetic proteins. Clin Orthop Releat Res 355:66–72

    Article  Google Scholar 

  33. Ristiniemi J, Flinkkila T, Hyvonen P, Lakovaara M, Pakarinen H, Jalovaara P (2007) RhBMP-7 accelerates the healing in distal tibial fractures treated by external fixation. J Bone Joint Surg 89:265–272

    Article  CAS  Google Scholar 

  34. Ronga M, Baldo F, Zappala G, Cherubino P (2006) Recombinant human bone morphogenetic protein-7 for treatment of long bone non-union: an observational, retrospective, non-randomized study of 105 patients. Injury 37(Suppl 3):S51–S56

    Article  PubMed  Google Scholar 

  35. Rothman RH, Klemek JS, Toton JJ (1971) The effect of iron deficiency anaemia on fracture healing. Clin Orthop Relat Res 77:276–283

    CAS  PubMed  Google Scholar 

  36. Spector JA, Mehrara BJ, Greenwald JA, Saadeh PB, Steinbrech DS, Bouletreau PJ, Smith LP, Longaker MT (2000) Osteoblast expression of vascular endothelial growth factor is modulated by the extracellular mircroenvironment. Am J Physiol Cell Physiol 280:72–80

    Google Scholar 

  37. Stinchfield FE, Sankaran B, Samilson R (1956) The effect of anticoagulant therapy on bone repair. J Bone Joint Surg A 38:270–282

    Google Scholar 

  38. Tonnensen PA, Heerfordt J, Pers M (1975) 150 open fractures of the tibial shaft: The relation between necrosis of the skin and delayed union. Acta Orthop Scand 46:823–835

    Article  Google Scholar 

  39. Uhthoff HK, Rahn BA (1981) Healing patterns of metaphyseal fractures. Clin Orthop Relat Res 160:295–303

    PubMed  Google Scholar 

  40. Walsh WR, Sherman P, Howlett CR, Sonnabend DH, Ehrlich MG (1997) Fracture healing in the rat osteopenia model. Clin Orthop Relat Res 342:218–227

    Article  PubMed  Google Scholar 

  41. Watson-Jones R (1955) Fractures an joint injuries. Churchill Livingstone, Edinburgh

    Google Scholar 

  42. Weiss S, Zimmermann G, Baumgart R, Kasten P, Bidlingmaier M, Henle P (2005) Systemic regulation of angiogenesis and matrix degradation in bone regeneration–distraction osteogenesis compared to rigid fracture healing. Bone 37:781–790

    Article  CAS  PubMed  Google Scholar 

  43. White AP, Weinstein MA, Patel TC, Horowitz MC, Friedlaender GE (2004) Lumbar arthrodesis gene expression: a comparison of autograft with osteogenic protein-1. Clin Orthop Relat Res 429:330–337

    Article  PubMed  Google Scholar 

  44. Zimmermann G, Henle P, Kusswetter M, Moghaddam A, Wentzensen A, Richter W, Weiss S (2005) TGF-beta1 as a marker of delayed fracture healing. Bone 36:779–785

    Article  CAS  PubMed  Google Scholar 

  45. Zimmermann G, Muller U, Loffler C, Wentzensen A, Moghaddam A (2007) Therapeutic outcome in tibial pseudarthrosis: bone morphogenetic protein 7 (BMP-7) versus autologous bone grafting for tibial fractures. Unfallchirurg 110:931–938

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. BG Trauma Center Ludwigshafen, Unfallchirurgische Klinik, University of Heidelberg, Ludwig, Guttmann, Str. 13, 67071, Ludwigshafen, Germany

    Arash Moghaddam, Charlotte Elleser, Bahram Biglari, Andreas Wentzensen & Gerald Zimmermann

Authors
  1. Arash Moghaddam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charlotte Elleser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bahram Biglari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andreas Wentzensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gerald Zimmermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arash Moghaddam.

Additional information

The protocol was formally approved by the ethics committee of "Landesärztekammer Mainz".

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moghaddam, A., Elleser, C., Biglari, B. et al. Clinical application of BMP 7 in long bone non-unions. Arch Orthop Trauma Surg 130, 71–76 (2010). https://doi.org/10.1007/s00402-009-0982-x

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00402-009-0982-x

Keywords

Search

Navigation