title: Recombinant human bone morphogenetic protein-2 in the treatment of bone fractures.
abstract: Over one million fractures occur per year in the US and are associated with impaired healing increasing patient morbidity, stress, and economic costs. Despite improvements in surgical technique, internal fixation, and understanding of biologics, fracture healing is delayed or impaired in up to 4% of all fractures. Complications due to impaired fracture healing present therapeutic challenges to the orthopedic surgeon and often lead to chronic functional and psychological disability for the patient. As a result, it has become clinically desirable to augment mechanical fixation with biologic strategies in order to accelerate osteogenesis and promote successful arthrodesis. The discovery of bone morphogenic protein (BMP) has been pivotal in understanding the biology of fracture healing and has been a source of intense clinical research as an adjunct to fracture treatment. Multiple in vitro and in vivo studies in animals have elucidated the complex biologic interactions between BMPs and cellular receptors and have convincingly demonstrated rhBMP-2 to be a safe, effective treatment option to enhance bone healing. Multiple clinical trials in trauma surgery have provided level 1 evidence for the use of rhBMP-2 as a safe and effective treatment of fractures. Human clinical trials have provided further insight into BMP-2 dosage, time course, carriers, and efficacy in fracture healing of tibial defects. These promising results have provided hope that a new biologic field of technology has emerged as a useful adjunct in the treatment of skeletal injuries and conditions.
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Ghodadra
authors.forename: Kern
authors.initials: K
authors.lastname: Singh
references.citation: Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S22-30
references.pmid: 9917623
references.citation: Eur J Endocrinol. 2000 Jan;142(1):9-21
references.pmid: 10633215
references.citation: J Bone Joint Surg Am. 2006 Jul;88(7):1431-41
references.pmid: 16818967
references.citation: Int Orthop. 2007 Dec;31(6):729-34
references.pmid: 17639384
references.citation: J Bone Miner Res. 1998 Sep;13(9):1483-90
references.pmid: 9738522
references.citation: J Orthop Sci. 2000;5(6):600-4
references.pmid: 11180925
references.citation: J Orthop Res. 1999 Mar;17(2):269-78
references.pmid: 10221845
references.citation: Cancer Res. 2003 May 15;63(10):2631-7
references.pmid: 12750290
references.citation: Biochem Biophys Res Commun. 2002 Sep 27;297(3):523-7
references.pmid: 12270126
references.citation: Curr Opin Genet Dev. 1994 Oct;4(5):737-44
references.pmid: 7849513
references.citation: J Cell Biol. 1994 Dec;127(6 Pt 1):1755-66
references.pmid: 7798324
references.citation: Clin Orthop Relat Res. 2002 Feb;(395):110-20
references.pmid: 11937870
references.citation: J Bone Joint Surg Am. 2005 Jun;87(6):1367-78
references.pmid: 15930551
references.citation: J Orthop Res. 2003 Nov;21(6):997-1004
references.pmid: 14554211
references.citation: J Bone Joint Surg Am. 2003 Aug;85(8):1425-35
references.pmid: 12925621
references.citation: J Bone Joint Surg Am. 1992 Sep;74(8):1162-71
references.pmid: 1400544
references.citation: J Am Acad Orthop Surg. 2005 Jan-Feb;13(1):77-86
references.pmid: 15712985
references.citation: J Bone Joint Surg Am. 2008 Feb;90 Suppl 1:48-54
references.pmid: 18292357
references.citation: Orthop Clin North Am. 1999 Oct;30(4):647-58
references.pmid: 10471769
references.citation: Acta Orthop Scand. 2000 Apr;71(2):160-7
references.pmid: 10852322
references.citation: J Clin Endocrinol Metab. 2001 Feb;86(2):875-80
references.pmid: 11158060
references.citation: Health Technol Assess. 2007 Aug;11(30):1-150, iii-iv
references.pmid: 17669279
references.citation: Bone. 1998 Jun;22(6):605-12
references.pmid: 9626398
references.citation: J Bone Joint Surg Am. 2002 Mar;84(3):454-64
references.pmid: 11886919
references.citation: J Bone Joint Surg Am. 2001 Aug;83(8):1219-30
references.pmid: 11507131
references.citation: J Bone Joint Surg Am. 2001;83-A Suppl 1(Pt 2):S79-81
references.pmid: 11314799
references.citation: J Bone Joint Surg Am. 2002 Dec;84(12):2123-34
references.pmid: 12473698
references.citation: J Bone Joint Surg Am. 2001 Jun;83(6):916-26
references.pmid: 11407801
references.citation: J Bone Miner Res. 1999 Nov;14(11):1805-15
references.pmid: 10571679
references.citation: Clin Orthop Relat Res. 2002 Apr;(397):119-26
references.pmid: 11953604
references.citation: Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S7-21
references.pmid: 9917622
references.citation: J Bone Joint Surg Am. 1995 Jun;77(6):940-56
references.pmid: 7782368
references.citation: Carcinogenesis. 2003 Sep;24(9):1445-54
references.pmid: 12819188
references.citation: Bone. 1998 Jun;22(6):591-603
references.pmid: 9626397
references.citation: J Bone Joint Surg Am. 2006 Jan;88(1):144-60
references.pmid: 16391260
references.citation: Nat Genet. 2006 Dec;38(12):1424-9
references.pmid: 17099713
references.citation: Growth Factors. 1993;9(1):57-71
references.pmid: 8347351
references.citation: J Cell Biol. 1991 May;113(3):681-7
references.pmid: 1849907
references.citation: J Bone Joint Surg Am. 2004 Jul;86(7):1425-38
references.pmid: 15252089
references.citation: Anticancer Drugs. 1998 Apr;9(4):327-31
references.pmid: 9635923
references.citation: J Bone Joint Surg Am. 2003 Aug;85(8):1544-52
references.pmid: 12925636
references.citation: J Bone Joint Surg Am. 2006 Jun;88(6):1258-65
references.pmid: 16757759
references.citation: J Bone Joint Surg Br. 1994 Jan;76(1):13-9
references.pmid: 8300656
references.citation: J Orthop Res. 2001 Mar;19(2):308-17
references.pmid: 11347706
references.citation: Biomaterials. 2001 Apr;22(7):725-30
references.pmid: 11246967
references.citation: Nature. 1994 Aug 4;370(6488):341-7
references.pmid: 8047140
references.citation: J Biomed Mater Res B Appl Biomater. 2005 Oct;75(1):137-45
references.pmid: 16035032
references.citation: J Hand Surg Am. 2000 Jan;25(1):19-28
references.pmid: 10642469
references.citation: J Bone Miner Res. 1995 Nov;10(11):1681-90
references.pmid: 8592944
references.citation: J Bone Joint Surg Am. 2006 Jul;88(7):1553-65
references.pmid: 16818982
references.citation: Anticancer Res. 2006 Jan-Feb;26(1A):293-8
references.pmid: 16475709
references.citation: Bone. 2002 Jul;31(1):158-64
references.pmid: 12110429
references.citation: Clin Orthop Relat Res. 1998 May;(350):18-25
references.pmid: 9602796
references.citation: J Bone Miner Res. 1991 Dec;6(12):1387-93
references.pmid: 1792947
references.citation: Clin Orthop Relat Res. 1999 Aug;(365):175-83
references.pmid: 10627702
references.citation: Bone. 1996 Jul;19(1 Suppl):1S-12S
references.pmid: 8830994
references.citation: Bone. 2003 Oct;33(4):628-37
references.pmid: 14555268
references.citation: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Dec;82(6):594-606
references.pmid: 8974129
references.citation: J Orthop Res. 2003 May;21(3):521-8
references.pmid: 12706026
references.citation: Endocrinology. 1995 Jun;136(6):2671-7
references.pmid: 7750491
references.citation: Clin Orthop Relat Res. 1998 Jan;(346):26-37
references.pmid: 9577407
references.citation: Gastroenterology. 1999 May;116(5):1202-16
references.pmid: 10220513
references.citation: J Bone Joint Surg Am. 1999 Jul;81(7):905-17
references.pmid: 10428121
references.citation: Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S132-47
references.pmid: 9917634
references.citation: Bull Hosp Jt Dis. 1997;56(1):63-72
references.pmid: 9063607
references.citation: J Biol Chem. 1992 Dec 15;267(35):25220-7
references.pmid: 1460021
references.citation: ANZ J Surg. 2007 Aug;77(8):626-31
references.pmid: 17635273
references.citation: J Orthop Res. 2001 Mar;19(2):318-27
references.pmid: 11347707
references.citation: Clin Orthop Relat Res. 1995 Jun;(315):119-28
references.pmid: 7634660
references.citation: Calcif Tissue Int. 1996 Apr;58(4):249-55
references.pmid: 8661956
references.citation: J Bone Miner Res. 2002 Feb;17(2):301-10
references.pmid: 11811561
references.citation: Clin Orthop Relat Res. 1995 Jun;(315):138-52
references.pmid: 7634662
references.citation: J Spinal Disord. 1998 Apr;11(2):95-101
references.pmid: 9588464
references.citation: Science. 1965 Nov 12;150(3698):893-9
references.pmid: 5319761