Skip to main content
Erschienen in: International Orthopaedics 6/2007

01.12.2007 | Review

Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery

verfasst von: Gavin B. Bishop, Thomas A. Einhorn

Erschienen in: International Orthopaedics | Ausgabe 6/2007

Einloggen, um Zugang zu erhalten

Abstract

Forty years after the discovery by Marshal R. Urist of a substance in bone matrix that has inductive properties for the development of bone and cartilage, there are now 15 individual human bone morphogenetic proteins (BMPs) that possess varying degrees of inductive activities. Two of these, BMP-2 and BMP-7, have become the subject of extensive research aimed at developing therapeutic strategies for the restoration and treatment of skeletal conditions. This has led to three different therapeutic preparations, each for a distinct clinical application. Non-union, open tibial fractures and spinal fusions are the three conditions for which there is clinical approval for use of BMPs. This article reviews the evidence supporting the therapeutic applications of BMPs as they are presently available and suggests future applications based on current research. Among the future directions discussed are percutaneous injections, protein carriers, advances in gene transfer technology and the use of BMPs to engineer the regeneration of skeletal parts.
Literatur
1.
Zurück zum Zitat The BMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) Study Group; Govender S, Csimma C, Genant HK, Valentin-Orpan A (2002) Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of 450 patients. J Bone Joint Surg -Am 84-A:2123–2134PubMed The BMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) Study Group; Govender S, Csimma C, Genant HK, Valentin-Orpan A (2002) Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of 450 patients. J Bone Joint Surg -Am 84-A:2123–2134PubMed
2.
Zurück zum Zitat Betz OB, Betz VM, Nazarian A, Pilapil CG, Vrahas MS, Bouxsein ML, Gerstenfeild LC, Einhorn TA, Evans CH (2006) Direct percutaneous gene delivery to enhance healing of segmental bone defects. J Bone Joint Surg Am 88:355–365PubMedCrossRef Betz OB, Betz VM, Nazarian A, Pilapil CG, Vrahas MS, Bouxsein ML, Gerstenfeild LC, Einhorn TA, Evans CH (2006) Direct percutaneous gene delivery to enhance healing of segmental bone defects. J Bone Joint Surg Am 88:355–365PubMedCrossRef
3.
Zurück zum Zitat Burkus JK, Transfeldt EE, Kitchel SH, Watkins RG, Balderston RA (2002) Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2. Spine 27:2396–2408PubMedCrossRef Burkus JK, Transfeldt EE, Kitchel SH, Watkins RG, Balderston RA (2002) Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2. Spine 27:2396–2408PubMedCrossRef
4.
Zurück zum Zitat Deutche Banc, Alex Brown (2001) Estimates and company information. February Deutche Banc, Alex Brown (2001) Estimates and company information. February
5.
Zurück zum Zitat Diefenderfer DL, Osyczka AM, Garino JP, Leboy PS (2003) Regulation of BMP-induced transcription in cultured human bone marrow stromal cells. J Bone Joint Surg -Am 85-A:19–28PubMed Diefenderfer DL, Osyczka AM, Garino JP, Leboy PS (2003) Regulation of BMP-induced transcription in cultured human bone marrow stromal cells. J Bone Joint Surg -Am 85-A:19–28PubMed
6.
Zurück zum Zitat Einhorn TA, Majeska RJ, Mohaideen A, Kagel EM, Bouxsein ML, Turek TJ, Wozney JM (2003) A single percutaneous injection of recombinant human bone morphogenetic protein-2 accelerates fracture repair. J Bone Joint Surg -Am 85-A:1425–1435PubMed Einhorn TA, Majeska RJ, Mohaideen A, Kagel EM, Bouxsein ML, Turek TJ, Wozney JM (2003) A single percutaneous injection of recombinant human bone morphogenetic protein-2 accelerates fracture repair. J Bone Joint Surg -Am 85-A:1425–1435PubMed
7.
Zurück zum Zitat Finkemeier CG (2002) Bone-grafting and bone graft substitute. J Bone Joint Surg -Am 84-A:454–464PubMed Finkemeier CG (2002) Bone-grafting and bone graft substitute. J Bone Joint Surg -Am 84-A:454–464PubMed
8.
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 83-A:151–158 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 83-A:151–158
9.
Zurück zum Zitat Khouri RK, Koudsi B, Reddi H (1991) Tissue transformation into bone in vivo. A potential practical application. JAMA 266:1953–1955PubMedCrossRef Khouri RK, Koudsi B, Reddi H (1991) Tissue transformation into bone in vivo. A potential practical application. JAMA 266:1953–1955PubMedCrossRef
10.
Zurück zum Zitat Kloen P, Di Paola M, Borens O, Richmond J, Perino G, Helfet DL, Goumans MJ (2003) BMP signaling components are expressed in human fracture callus. Bone 33:362–371PubMedCrossRef Kloen P, Di Paola M, Borens O, Richmond J, Perino G, Helfet DL, Goumans MJ (2003) BMP signaling components are expressed in human fracture callus. Bone 33:362–371PubMedCrossRef
11.
Zurück zum Zitat Musculoskeletal injuries report: incidence, risk factors and prevention. American Academy of Orthopaedic Surgeons (2000) researchinfo@aaos.org Musculoskeletal injuries report: incidence, risk factors and prevention. American Academy of Orthopaedic Surgeons (2000) researchinfo@aaos.org
12.
Zurück zum Zitat National Trauma Data Bank Report (2002) The American College of Surgeons National Trauma Data Bank Report (2002) The American College of Surgeons
13.
Zurück zum Zitat Pecina M, Giltaij LR, Vukicevic S (2001) Orthopaedic applications of osteogenic protein-1 (BMP-7). Int Orthop 25:203–208PubMedCrossRef Pecina M, Giltaij LR, Vukicevic S (2001) Orthopaedic applications of osteogenic protein-1 (BMP-7). Int Orthop 25:203–208PubMedCrossRef
14.
Zurück zum Zitat Pecina M, Haspl M, Jelic M, Vukicevic S (2003) Repair of a resistant tibia non-union with a recombinant bone morphogenetic protein-7 (rh-BMP-7). Int Orthop 27:320–321PubMedCrossRef Pecina M, Haspl M, Jelic M, Vukicevic S (2003) Repair of a resistant tibia non-union with a recombinant bone morphogenetic protein-7 (rh-BMP-7). Int Orthop 27:320–321PubMedCrossRef
15.
Zurück zum Zitat Seeherman HJ, Bouxsein ML, Kim H, Li R, Li XJ, Aiolova M, Wozney JM (2004) Recombinant human bone morphogenetic protein-2 delivered in an injectable calcium phosphate paste accelerates osteotomy-site healing in a nonhuman primate model. J Bone Joint Surg -Am 86-A:1961–1972PubMed Seeherman HJ, Bouxsein ML, Kim H, Li R, Li XJ, Aiolova M, Wozney JM (2004) Recombinant human bone morphogenetic protein-2 delivered in an injectable calcium phosphate paste accelerates osteotomy-site healing in a nonhuman primate model. J Bone Joint Surg -Am 86-A:1961–1972PubMed
16.
Zurück zum Zitat Seeherman HJ, Li R, Bouxsein ML, Kim H, Li XJ, Smith-Adaline EA, Aiolova M, Wozney JM (2006) rhBMP-2/Calcium phosphate matrix accelerates osteotomy- site healing in a nonhuman primate model at multiple treatment times and concentrations. J Bone Joint Surg -Am 88:144–160PubMedCrossRef Seeherman HJ, Li R, Bouxsein ML, Kim H, Li XJ, Smith-Adaline EA, Aiolova M, Wozney JM (2006) rhBMP-2/Calcium phosphate matrix accelerates osteotomy- site healing in a nonhuman primate model at multiple treatment times and concentrations. J Bone Joint Surg -Am 88:144–160PubMedCrossRef
17.
Zurück zum Zitat Shafritz A, Shore EM, Gannon FH, Zasloff MA, Taub R, Muenke M, Kaplan FS (1996) Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. N Engl J Med 335:555–561PubMedCrossRef Shafritz A, Shore EM, Gannon FH, Zasloff MA, Taub R, Muenke M, Kaplan FS (1996) Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. N Engl J Med 335:555–561PubMedCrossRef
18.
Zurück zum Zitat Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Brown MA, Kaplan FS (2006) A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38:525–527PubMedCrossRef Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Brown MA, Kaplan FS (2006) A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38:525–527PubMedCrossRef
19.
Zurück zum Zitat Swiontkowski MF, Aro HT, Donell S, Esterhai JL, Goulet J, Jones A, Kregor PJ, Nordsletten L, Paiement G, Patel A (2006) Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J Bone Joint Surg -Am 88:1258–1265PubMedCrossRef Swiontkowski MF, Aro HT, Donell S, Esterhai JL, Goulet J, Jones A, Kregor PJ, Nordsletten L, Paiement G, Patel A (2006) Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J Bone Joint Surg -Am 88:1258–1265PubMedCrossRef
21.
Zurück zum Zitat Urist MR (1980) Bone transplants and implants. Lippencott, Philadelphia Pennsylvania Urist MR (1980) Bone transplants and implants. Lippencott, Philadelphia Pennsylvania
22.
Zurück zum Zitat Warnke PH, Springer IN, Wiltfang J, Acil Y, Eufinger H, Mehmoller M, Russo PAJ, Bolte H, Sherry E, Behrens E, Terheyden H (2004) Growth and transplantation of a custom vascularised bone graft in a man. Lancet 364:766–770PubMedCrossRef Warnke PH, Springer IN, Wiltfang J, Acil Y, Eufinger H, Mehmoller M, Russo PAJ, Bolte H, Sherry E, Behrens E, Terheyden H (2004) Growth and transplantation of a custom vascularised bone graft in a man. Lancet 364:766–770PubMedCrossRef
23.
Zurück zum Zitat Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA (1988) Novel regulators of bone formation: molecular clones and activities. Science 242:1528–1534PubMedCrossRef Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA (1988) Novel regulators of bone formation: molecular clones and activities. Science 242:1528–1534PubMedCrossRef
24.
Zurück zum Zitat Ziran BH, Smith WR, Lahti Z, Williams A (2004) Use of calcium-based demineralized bone matrix (DBM) allograft product for nonunions and posttraumatic reconstruction of the appendicular skeleton: preliminary results and complications. Orthopaedic Trauma Association Annual Meeting, Oct 8–10th, 2004, Paper #64 Ziran BH, Smith WR, Lahti Z, Williams A (2004) Use of calcium-based demineralized bone matrix (DBM) allograft product for nonunions and posttraumatic reconstruction of the appendicular skeleton: preliminary results and complications. Orthopaedic Trauma Association Annual Meeting, Oct 8–10th, 2004, Paper #64
Metadaten
Titel
Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery
verfasst von
Gavin B. Bishop
Thomas A. Einhorn
Publikationsdatum
01.12.2007
Verlag
Springer-Verlag
Erschienen in
International Orthopaedics / Ausgabe 6/2007
Print ISSN: 0341-2695
Elektronische ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-007-0424-8

Weitere Artikel der Ausgabe 6/2007

International Orthopaedics 6/2007 Zur Ausgabe

Arthropedia

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

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

28.05.2024 Traumatologische Notfälle Nachrichten

In der Notaufnahme wird die Chance, Opfer von häuslicher Gewalt zu identifizieren, von Orthopäden und Orthopädinnen offenbar zu wenig genutzt. Darauf deuten die Ergebnisse einer Fragebogenstudie an der Sahlgrenska-Universität in Schweden hin.

Fehlerkultur in der Medizin – Offenheit zählt!

Darüber reden und aus Fehlern lernen, sollte das Motto in der Medizin lauten. Und zwar nicht nur im Sinne der Patientensicherheit. Eine negative Fehlerkultur kann auch die Behandelnden ernsthaft krank machen, warnt Prof. Dr. Reinhard Strametz. Ein Plädoyer und ein Leitfaden für den offenen Umgang mit kritischen Ereignissen in Medizin und Pflege.

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

Update Orthopädie und Unfallchirurgie

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