Skip to main content
Erschienen in: Archives of Orthopaedic and Trauma Surgery 1/2010

01.01.2010 | Trauma Surgery

Clinical application of BMP 7 in long bone non-unions

verfasst von: Arash Moghaddam, Charlotte Elleser, Bahram Biglari, Andreas Wentzensen, Gerald Zimmermann

Erschienen in: Archives of Orthopaedic and Trauma Surgery | Ausgabe 1/2010

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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 51:595–600CrossRef 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 51:595–600CrossRef
2.
Zurück zum Zitat Augat P, Merk J, Ingnatius A et al (1996) Early, full weight-bearing with flexible fixation delays fracture healing. Clin Orthop Relat Res 328:194–202CrossRefPubMed Augat P, Merk J, Ingnatius A et al (1996) Early, full weight-bearing with flexible fixation delays fracture healing. Clin Orthop Relat Res 328:194–202CrossRefPubMed
3.
Zurück zum Zitat Bergmann A, Schwarz BHM (1989) Cause, prognosis and therapy of tibial pseudarthroses. Aktuelle Traumatol 19:205–208PubMed Bergmann A, Schwarz BHM (1989) Cause, prognosis and therapy of tibial pseudarthroses. Aktuelle Traumatol 19:205–208PubMed
4.
Zurück zum Zitat Brinker MR, Bailey DE Jr (1997) Fracture healing in tibia fractures with an associated vascular injury. J Trauma 42:11–19CrossRefPubMed Brinker MR, Bailey DE Jr (1997) Fracture healing in tibia fractures with an associated vascular injury. J Trauma 42:11–19CrossRefPubMed
5.
Zurück zum Zitat 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 19:151–157CrossRefPubMed 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 19:151–157CrossRefPubMed
6.
Zurück zum Zitat 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 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
7.
Zurück zum Zitat 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 15:577–584CrossRefPubMed 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 15:577–584CrossRefPubMed
8.
Zurück zum Zitat 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 337:198–207CrossRef 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 337:198–207CrossRef
9.
Zurück zum Zitat Cruess RL, Sakai T (1972) The effect of cortisone upon synthesis rates of some components of rat bone matrix. Clin Orthop Relat Res 86:253–259CrossRefPubMed Cruess RL, Sakai T (1972) The effect of cortisone upon synthesis rates of some components of rat bone matrix. Clin Orthop Relat Res 86:253–259CrossRefPubMed
10.
Zurück zum Zitat Daftari TK, Whitesides TE, Heller JG et al (1994) Nicotine on the revascularization of bone graft: an experimental study in rabbits. Spine 19:904–911CrossRefPubMed Daftari TK, Whitesides TE, Heller JG et al (1994) Nicotine on the revascularization of bone graft: an experimental study in rabbits. Spine 19:904–911CrossRefPubMed
11.
Zurück zum Zitat Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res 355S:7–21CrossRef Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res 355S:7–21CrossRef
12.
Zurück zum Zitat 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 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
13.
Zurück zum Zitat 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 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
14.
Zurück zum Zitat 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 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
15.
Zurück zum Zitat 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 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
16.
Zurück zum Zitat 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 81:710–718CrossRefPubMed 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 81:710–718CrossRefPubMed
17.
Zurück zum Zitat Gelberman RH, Menon J (1980) The vascularity of the scaphoid bone. J Hand Surg 5:508–513 Gelberman RH, Menon J (1980) The vascularity of the scaphoid bone. J Hand Surg 5:508–513
18.
Zurück zum Zitat Giannoudis PV, Tzioupis C (2005) Clinical applications of BMP-7. The UK perspective. Injury 36S:47–50CrossRef Giannoudis PV, Tzioupis C (2005) Clinical applications of BMP-7. The UK perspective. Injury 36S:47–50CrossRef
19.
Zurück zum Zitat 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 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
20.
Zurück zum Zitat Hayda RA, Brighton CT, Esterhai JL (1998) Pathophysiology of delayed healing. Clin Orthop Relat Res 355S:31–40CrossRef Hayda RA, Brighton CT, Esterhai JL (1998) Pathophysiology of delayed healing. Clin Orthop Relat Res 355S:31–40CrossRef
21.
Zurück zum Zitat Healy WL, White GM, Mick CA et al (1987) Nonunion of the humeral shaft. Clin Orthop Relat Res 219:206–213PubMed Healy WL, White GM, Mick CA et al (1987) Nonunion of the humeral shaft. Clin Orthop Relat Res 219:206–213PubMed
22.
Zurück zum Zitat Henle P, Zimmermann G, Weiss S (2005) Matrix metalloproteinases and failed fracture healing. Bone 37:791–798CrossRefPubMed Henle P, Zimmermann G, Weiss S (2005) Matrix metalloproteinases and failed fracture healing. Bone 37:791–798CrossRefPubMed
23.
Zurück zum Zitat 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 54:969–979CrossRefPubMed 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 54:969–979CrossRefPubMed
24.
Zurück zum Zitat Kwiatkowski TC, Hanley JEN, Ramp WK (1996) Cigarette smoking and its orthopaedic consequences. Am J Orthop 25:590–597PubMed Kwiatkowski TC, Hanley JEN, Ramp WK (1996) Cigarette smoking and its orthopaedic consequences. Am J Orthop 25:590–597PubMed
25.
Zurück zum Zitat Larson RL, Sukkivan CR, Janes JM (1961) Trauma surgery and the circulation of the talus: what are the risks of avascular necrosis? J Trauma 1:13–21CrossRef Larson RL, Sukkivan CR, Janes JM (1961) Trauma surgery and the circulation of the talus: what are the risks of avascular necrosis? J Trauma 1:13–21CrossRef
26.
Zurück zum Zitat Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. J Bone Joint Surg Am 84-A:1032–1044PubMed Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. J Bone Joint Surg Am 84-A:1032–1044PubMed
27.
Zurück zum Zitat 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 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
28.
Zurück zum Zitat McKee MD (2005) Recombinant human bone morphogenic protein-7: applications for clinical trauma. J Orthop Trauma 19:S26–S28CrossRefPubMed McKee MD (2005) Recombinant human bone morphogenic protein-7: applications for clinical trauma. J Orthop Trauma 19:S26–S28CrossRefPubMed
29.
Zurück zum Zitat Nelson GE, Kelly PJ, Peterson F et al (1960) Blood supply of the human tibia. J Bone Joint Surg A 42:625–635 Nelson GE, Kelly PJ, Peterson F et al (1960) Blood supply of the human tibia. J Bone Joint Surg A 42:625–635
30.
Zurück zum Zitat Nunamaker DM (1998) Experimental models of fracture repair. Clin Orthop Releat Res 355S:56–65CrossRef Nunamaker DM (1998) Experimental models of fracture repair. Clin Orthop Releat Res 355S:56–65CrossRef
31.
Zurück zum Zitat 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 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
32.
Zurück zum Zitat Reddi AH (1998) Initiation of fracture repair by bone morphogenetic proteins. Clin Orthop Releat Res 355:66–72CrossRef Reddi AH (1998) Initiation of fracture repair by bone morphogenetic proteins. Clin Orthop Releat Res 355:66–72CrossRef
33.
Zurück zum Zitat 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 89:265–272CrossRef 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 89:265–272CrossRef
34.
Zurück zum Zitat 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–S56CrossRefPubMed 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–S56CrossRefPubMed
35.
Zurück zum Zitat Rothman RH, Klemek JS, Toton JJ (1971) The effect of iron deficiency anaemia on fracture healing. Clin Orthop Relat Res 77:276–283PubMed Rothman RH, Klemek JS, Toton JJ (1971) The effect of iron deficiency anaemia on fracture healing. Clin Orthop Relat Res 77:276–283PubMed
36.
Zurück zum Zitat 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 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
37.
Zurück zum Zitat Stinchfield FE, Sankaran B, Samilson R (1956) The effect of anticoagulant therapy on bone repair. J Bone Joint Surg A 38:270–282 Stinchfield FE, Sankaran B, Samilson R (1956) The effect of anticoagulant therapy on bone repair. J Bone Joint Surg A 38:270–282
38.
Zurück zum Zitat 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 46:823–835CrossRef 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 46:823–835CrossRef
39.
Zurück zum Zitat Uhthoff HK, Rahn BA (1981) Healing patterns of metaphyseal fractures. Clin Orthop Relat Res 160:295–303PubMed Uhthoff HK, Rahn BA (1981) Healing patterns of metaphyseal fractures. Clin Orthop Relat Res 160:295–303PubMed
40.
Zurück zum Zitat Walsh WR, Sherman P, Howlett CR, Sonnabend DH, Ehrlich MG (1997) Fracture healing in the rat osteopenia model. Clin Orthop Relat Res 342:218–227CrossRefPubMed Walsh WR, Sherman P, Howlett CR, Sonnabend DH, Ehrlich MG (1997) Fracture healing in the rat osteopenia model. Clin Orthop Relat Res 342:218–227CrossRefPubMed
41.
Zurück zum Zitat Watson-Jones R (1955) Fractures an joint injuries. Churchill Livingstone, Edinburgh Watson-Jones R (1955) Fractures an joint injuries. Churchill Livingstone, Edinburgh
42.
Zurück zum Zitat 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 37:781–790CrossRefPubMed 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 37:781–790CrossRefPubMed
43.
Zurück zum Zitat 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 429:330–337CrossRefPubMed 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 429:330–337CrossRefPubMed
44.
Zurück zum Zitat 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 36:779–785CrossRefPubMed 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 36:779–785CrossRefPubMed
45.
Zurück zum Zitat 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 110:931–938CrossRefPubMed 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 110:931–938CrossRefPubMed
Metadaten
Titel
Clinical application of BMP 7 in long bone non-unions
verfasst von
Arash Moghaddam
Charlotte Elleser
Bahram Biglari
Andreas Wentzensen
Gerald Zimmermann
Publikationsdatum
01.01.2010
Verlag
Springer-Verlag
Erschienen in
Archives of Orthopaedic and Trauma Surgery / Ausgabe 1/2010
Print ISSN: 0936-8051
Elektronische ISSN: 1434-3916
DOI
https://doi.org/10.1007/s00402-009-0982-x

Weitere Artikel der Ausgabe 1/2010

Archives of Orthopaedic and Trauma Surgery 1/2010 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.