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Growth factors in orthopaedic surgery: demineralized bone matrix versus recombinant bone morphogenetic proteins

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Abstract

During recent decades the utilisation of growth factors, especially BMPs, has received an increasing interest in orthopaedic surgery. For clinical implantation the two main options are demineralised bone matrix (DBM) and recombinant bone morphogenetic proteins (rhBMP). Many clinical studies agree on an equivalent osteoinductive effect between DBM, BMPs and autologous bone graft; however, the different origins and processing of DBM and rhBMP may introduce some fluctuations. Their respective characteristics are reviewed and possible interactions with their effectiveness are analysed. The main difference concerns the concentration of BMPs, which varies to an order of magnitude of 106 between DBM and rhBMPs. This may explain the variability in efficiency of some products and the adverse effects. Currently, considering osteoinductive properties, safety and availability, the DBM seems to offer several advantages. However, if DBM and rhBMPs are useful in some indications, their effectiveness and safety can be improved and more evidence-based studies are needed to better define the indications.

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References

  1. Pecina M, Vukicevic S (2007) Biological aspects of bone, cartilage and tendon regeneration. Int Orthop 31(6):719–20

    Article  PubMed Central  PubMed  Google Scholar 

  2. Pećina M, Vukičević S (2014) Tissue engineering and regenerative orthopaedics (TERO). Int Orthop 38(9):1757–60

    Article  PubMed  Google Scholar 

  3. Devescovi V, Leonardi E, Ciapetti G, Cenni E (2008) Growth factors in bone repair. Chir Organi Mov 92(3):161–8

    Article  PubMed  Google Scholar 

  4. Ghodadra N, Singh K (2008) Recombinant human bone morphogenetic protein-2 in the treatment of bone fractures. Biogeosciences 2(3):345–54

    CAS  Google Scholar 

  5. Gruskin E, Doll B, Futrell F, Schmitz J, Hollinger J (2012) Demineralized bone matrix in bone repair: history and use. Adv Drug Deliv Rev 64(12):1063–77

    Article  CAS  PubMed  Google Scholar 

  6. Lissenberg-Thunnissen S, de Gorter D, Sier C, Schipper I (2011) Use and efficacy of bone morphogenetic proteins in fracture healing. Int Orthop 35(9):1271–80

    Article  PubMed Central  PubMed  Google Scholar 

  7. Veillette C, McKee M (2007) Growth factors–BMPs, DBMs, and buffy coat products: are there any proven differences amongst them? Injury 38(Suppl 1):S38–48

    Article  PubMed  Google Scholar 

  8. Holt D, Grainger D (2012) Demineralized bone matrix as a vehicle for delivering endogenous and exogenous therapeutics in bone repair. Adv Drug Deliv Rev 64(12):1123–8

    Article  CAS  PubMed  Google Scholar 

  9. Wildemann B, Kadow-Romacker A, Pruss A, Haas N, Schmidmaier G (2007) Quantification of growth factors in allogenic bone grafts extracted with three different methods. Cell Tissue Bank 8(2):107–14

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Wildemann B, Kadow-Romacker A, Haas N, Schmidmaier G (2007) Quantification of various growth factors in different demineralized bone matrix preparations. J Biomed Mater Res A 81(2):437–42

    Article  CAS  PubMed  Google Scholar 

  11. Lacroix P (1945) Recent investigations on the growth of bone. Nature 156:576

    Article  Google Scholar 

  12. Lacroix P (1947) Organizers and the growth of bones. J Bone Joint Surg Am 29(2):292–6

    CAS  PubMed  Google Scholar 

  13. Urist M (1965) Bone: formation by autoinduction. Science 12;150(3698):893–9

    Article  Google Scholar 

  14. Urist M, Strates B (1971) Bone morphogenetic protein. J Dent Res 50(6):1392–406

    Article  CAS  PubMed  Google Scholar 

  15. Sampath T, Reddi A (1981) Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. Proc Natl Acad Sci USA 78(12):7599–603

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Muthukumaran N, Ma S, Reddi A (1988) Dose-dependence of and threshold for optimal bone induction by collagenous bone matrix and osteogenin-enriched fraction. Coll Relat Res 8(5):433–41

    Article  CAS  PubMed  Google Scholar 

  17. Bessa P, Casal M, Reis R (2008) Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med 2(1):1–13

    Article  CAS  PubMed  Google Scholar 

  18. Vukicevic S, Oppermann H, Verbanac D, Jankolija M, Popek I, Curak J, Brkljacic J, Pauk M, Erjavec I, Francetic I, Dumic-Cule I, Jelic M, Durdevic D, Vlahovic T, Novak R, Kufner V, Bordukalo Niksic T, Kozlovic M, Banic Tomisic Z, Bubic-Spoljar J, Bastalic I, Vikic-Topic S, Peric M, Pecina M, Grgurevic L (2014) The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing. Int Orthop 38(3):635–47

    Article  PubMed  Google Scholar 

  19. Cho T, Gerstenfeld L, Einhorn T (2002) Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res 17(3):513–20

    Article  CAS  PubMed  Google Scholar 

  20. Cheng H, Jiang W, Phillips F, Haydon R, Peng Y, Zhou L, Luu H, An N, Breyer B, Vanichakarn P, Szatkowski J, Park J, He T (2003) Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 85-A(8):1544–52

    PubMed  Google Scholar 

  21. Yu Y, Lieu S, Lu C, Miclau T, Marcucio RS, Colnot C (2010) Immunolocalization of BMPs, BMP antagonists, receptors, and effectors during fracture repair. Bone 46(3):841–51

    Article  CAS  PubMed  Google Scholar 

  22. Yu Y, Lieu S, Lu C, Colnot C (2010) Bone morphogenetic protein 2 stimulates endochondral ossification by regulating periosteal cell fate during bone repair. Bone 47(1):65–73

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Carnes DL, De La Fontaine J, Cochran DL, Mellonig JT, Keogh B, Harris SE, Ghosh-Choudhury N, Dean DD, Boyan BD, Schwartz Z (1999) Evaluation of 2 novel approaches for assessing the ability of demineralized freeze-dried bone allograft to induce new bone formation. J Periodontol 70(4):353–63

    Article  PubMed  Google Scholar 

  24. Glowacki J (2005) A review of osteoinductive testing methods and sterilization processes for demineralized bone. Cell Tissue Bank 6(1):3–12

    Article  PubMed  Google Scholar 

  25. Vaziri S, Vahabi S, Torshabi M, Hematzadeh S (2012) In vitro assay for osteoinductive activity of different demineralized freeze-dried bone allograft. J Periodontal Implant Sci 42(6):224–30

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Hierholzer C, Sama D, Toro B, Peterson M, Helfet L (2006) Plate fixation of ununited humeral shaft fractures: effect of type of bone graft on healing. J Bone Joint Surg Am 88(7):1442–7

    Article  PubMed  Google Scholar 

  27. Pieske O, Wittmann A, Zaspel J, Löffler T, Rubenbauer B, Trentzsch H, Piltz S (2009) Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones. J Trauma Manag Outcomes 15(3):11

  28. Sassard W, Eidman D, Gray P, Block J, Russo R, Russell J, Taboada E (2000) Augmenting local bone with Grafton demineralized bone matrix for posterolateral lumbar spine fusion: avoiding second site autologous bone harvest. Orthopedics 23(10):1059–64

    CAS  PubMed  Google Scholar 

  29. Cammisa F, Lowery G, Garfin S, Geisler F, Klara P, McGuire R, Sassard W, Stubbs H, Block J (2004) Two-year fusion rate equivalency between Grafton DBM gel and autograft in posterolateral spine fusion: a prospective controlled trial employing a side-by-side comparison in the same patient. Spine 29(6):660–6

    Article  PubMed  Google Scholar 

  30. Schizas C, Triantafyllopoulos D, Kosmopoulos V, Tzinieris N, Stafylas K (2008) Posterolateral lumbar spine fusion using a novel demineralized bone matrix: a controlled case pilot study. Arch Orthop Trauma Surg 128(6):621–5

    Article  PubMed  Google Scholar 

  31. Kang J, An H, Hilibrand A, Yoon S, Kavanagh E, Boden S (2012) Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions. Spine 37(12):1083–91

    Article  PubMed  Google Scholar 

  32. Aghdasi B, Montgomery SR, Daubs MD, Wang JC (2013) A review of demineralized bone matrices for spinal fusion: the evidence for efficacy. Surgeon 11(1):39–48

    Article  CAS  PubMed  Google Scholar 

  33. Tilkeridis K, Touzopoulos P, Ververidis A, Christodoulou S, Kazakos K, Drosos G (2014) Use of demineralized bone matrix in spinal fusion. World J Orthop 5(1):30–37

    Article  PubMed Central  PubMed  Google Scholar 

  34. Geesink R, Hoefnagels N, Bulstra S (1999) Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect. J Bone Joint Surg (Br) 81(4):710–8

    Article  CAS  Google Scholar 

  35. Govender S, Csimma C, Genant H, Valentin-Opran A, Amit Y, Arbel R, Aro H et al (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 84-A(12):2123–34

    PubMed  Google Scholar 

  36. Wenisch S, Trinkaus K, Hild A, Hose D, Herde K, Heiss C, Kilian O, Alt V, Schnettler R (2005) Human reaming debris: a source of multipotent stem cells. Bone 36(1):74–83

    Article  PubMed  Google Scholar 

  37. Schmidmaier G, Herrmann S, Green J, Weber T, Scharfenberger A, Haas N, Wildemann B (2006) Quantitative assessment of growth factors in reaming aspirate, iliac crest, and platelet preparation. Bone 39(5):1156–63

    Article  CAS  PubMed  Google Scholar 

  38. Giannoudis P, Pountos I, Morley J, Perry S, Tarkin H, Pape H (2008) Growth factor release following femoral nailing. Bone 42(4):751–7

    Article  CAS  PubMed  Google Scholar 

  39. Aro H, Govender S, Patel A, Hernigou P, Perera de Gregorio A, Popescu G, Golden J, Christensen J, Valentin A (2011) Recombinant human bone morphogenetic protein-2: a randomized trial in open tibial fractures treated with reamed nail fixation. J Bone Joint Surg Am 93(9):801–8

    Article  PubMed  Google Scholar 

  40. Friedlaender G, Perry C, Cole J, Cook S, Cierny G, Muschler G, Zych G, Calhoun J, LaForte A, Yin S (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am83-A Suppl 1(Pt 2):S151–8

    Google Scholar 

  41. Maniscalco P, Gambera D, Bertone C, Rivera F, Crainz E, Urgelli S (2002) Healing of fresh tibial fractures with OP-1. A preliminary report Acta Biomed 73(1–2):27–33

    Google Scholar 

  42. Singh K, Smucker J, Gill S, Boden S (2006) Use of recombinant human bone morphogenetic protein-2 as an adjunct in posterolateral lumbar spine fusion: a prospective CT-scan analysis at one and two years. J Spinal Disord Tech 19(6):416–23

    Article  PubMed  Google Scholar 

  43. Abdullah K, Steinmetz M, Benzel E, Mroz T (2011) The state of lumbar fusion extenders. Spine 36(20):E1328–34

    Article  PubMed  Google Scholar 

  44. Stambough J, Clouse E, Stambough J (2010) Instrumented one and two level posterolateral fusions with recombinant human bone morphogenetic protein-2 and allograft: a computed tomography study. Spine 35(1):124–9

    Article  PubMed  Google Scholar 

  45. Carragee E, Ghanayem A, Weiner B, Rothman D, Bono C (2011) A challenge to integrity in spine publications: years of living dangerously with the promotion of bone growth factors. Spine J 11(6):463–8

    Article  PubMed  Google Scholar 

  46. Carragee E, Hurwitz E, Weiner B (2011) A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 11(6):471–91

    Article  PubMed  Google Scholar 

  47. Rodgers M, Brown J, Heirs M, Higgins J, Mannion R, Simmonds M, Stewart L (2013) Reporting of industry funded study outcome data: comparison of confidential and published data on the safety and effectiveness of rhBMP-2 for spinal fusion. BMJ 346:f3981

    Article  PubMed Central  PubMed  Google Scholar 

  48. Carragee E, Mitsunaga K, Hurwitz E, Scuderi G (2011) Retrograde ejaculation after anterior lumbar interbody fusion using rhBMP-2: a cohort controlled study. Spine J 11(6):511–6

    Article  PubMed  Google Scholar 

  49. Vaidya R, Sethi A, Bartol S, Jacobson M, Coe C, Craig J (2008) Complications in the use of rhBMP-2 in PEEK cages for interbody spinal fusions. J Spinal Disord Tech 21(8):557–62

    Article  PubMed  Google Scholar 

  50. Carragee E, Wildstein M (2007) A controlled trial of BMP and unilateral transpedicular instrumentation in circumferential single or double level lumbar fusion. Proceedings of the 22nd annual meeting of the North American Spine Society. Spine J 7(5):8S–9S

    Article  Google Scholar 

  51. Vaidya R, Carp J, Sethi A, Bartol S, Craig J, Les C (2007) Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2. Eur Spine J 16(8):1257–65

    Article  PubMed Central  PubMed  Google Scholar 

  52. Meisel H, Schnöring M, Hohaus C, Minkus Y, Beier A, Ganey T, Mansmann U (2008) Posterior lumbar interbody fusion using rhBMP-2. Eur Spine J 17(12):1735–44

    Article  PubMed Central  PubMed  Google Scholar 

  53. Rihn J, Makda J, Hong J, Patel R, Hilibrand A, Anderson D, Vaccaro A, Albert T (2009) The use of RhBMP-2 in single-level transforaminal lumbar interbody fusion: a clinical and radiographic analysis. Eur Spine J 18(11):1629–36

    Article  PubMed Central  PubMed  Google Scholar 

  54. Buttermann G (2008) Prospective nonrandomized comparison of an allograft with bone morphogenic protein versus an iliac-crest autograft in anterior cervical discectomy and fusion. Spine J 8(3):426–35

    Article  PubMed  Google Scholar 

  55. Perri B, Cooper M, Lauryssen C, Anand N (2007) Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy and fusion: a case study. Spine J 7(2):235–9

    Article  PubMed  Google Scholar 

  56. Glassman S, Gum J, Crawford C, Shields C, Carreon L (2011) Complications with recombinant human bone morphogenetic protein-2 in posterolateral spine fusion associated with a dural tear. Spine J 11(6):522–6

    Article  PubMed  Google Scholar 

  57. Smucker J, Rhee J, Singh K, Yoon S, Heller J (2006) Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine. Spine 31(24):2813–9

    Article  PubMed  Google Scholar 

  58. Fu R, Selph S, McDonagh M, Peterson K, Tiwari A, Chou R, Helfand M (2013) Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis. Ann Intern Med 158(12):890–902

    Article  PubMed  Google Scholar 

  59. Simmonds M, Brown J, Heirs M, Higgins J, Mannion R, Rodgers M, Stewart L (2013) Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data. Ann Intern Med 158(12):877–89

    Article  PubMed  Google Scholar 

  60. Adams CL, Ogden K, Robertson IK, Broadhurst S, Edis D (2014) Effectiveness and safety of recombinant human bone morphogenetic protein-2 versus local bone graft in primary lumbar interbody fusions. Spine 39(2):164–71

    Article  PubMed  Google Scholar 

  61. Michielsen J, Sys J, Rigaux A, Bertrand C (2013) The effect of recombinant human bone morphogenetic protein-2 in single-level posterior lumbar interbody arthrodesis. J Bone Joint Surg Am 95(10):873–80

    Article  CAS  PubMed  Google Scholar 

  62. AAOS (2010) Summary of typical bone-graft substitutes that are commercially available – 2010. http://www.aatb.org/aatb/files/ccLibraryFiles/Filename/000000000323/BoneGraftSubstituteTable2010.pdf Accessed 12 September 2014

  63. Schwartz Z, Somers A, Mellonig JT, Carnes DL, Dean DD, Cochran DL, Boyan BD (1998) Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender. J Periodontol 69(4):470–8

    Article  CAS  PubMed  Google Scholar 

  64. Zhang M, Powers RM, Wolfinbarger L (1997) Effect(s) of the demineralization process on the osteoinductivity of demineralized bone matrix. J Periodontol 68(11):1085–92

    Article  CAS  PubMed  Google Scholar 

  65. Pietrzak WS, Woodell-May J, McDonald N (2006) Assay of bone morphogenetic protein-2, -4, and -7 in human demineralized bone matrix. J Craniofac Surg 17(1):84–90

    Article  PubMed  Google Scholar 

  66. Honsawek S, Powers RM, Wolfinbarger L (2005) Extractable bone morphogenetic protein and correlation with induced new bone formation in an in vivo assay in the athymic mouse model. Cell Tissue Bank 6(1):13–23

    Article  CAS  PubMed  Google Scholar 

  67. Lohmann CH, Andreacchio D, Köster G, Carnes DL, Cochran DL, Dean DD, Boyan BD, Schwartz Z (2001) Tissue response and osteoinduction of human bone grafts in vivo. Arch Orthop Trauma Surg 121(10):583–90

    Article  CAS  PubMed  Google Scholar 

  68. Traianedes K, Russell JL, Edwards JT, Stubbs HA, Shanahan IR, Knaack D (2004) Donor age and gender effects on osteoinductivity of demineralized bone matrix. J Biomed Mater Res B Appl Biomater 70(1):21–9

    Article  PubMed  Google Scholar 

  69. Bessho K, Kusumoto K, Fujimura K, Konishi Y, Ogawa Y, Tani Y, Iizuka T (1999) Comparison of recombinant and purified human bone morphogenetic protein. Br J Oral Maxillofac Surg 37(1):2–5

    Article  CAS  PubMed  Google Scholar 

  70. Aono A, Hazama M, Notoya K, Taketomi S, Yamasaki H, Tsukuda R, Sasaki S, Fujisawa Y (1995) Potent ectopic bone-inducing activity of bone morphogenetic protein-4/7 heterodimer. Biochem Biophys Res Commun 210(3):670–7

    Article  CAS  PubMed  Google Scholar 

  71. Israel DI, Nove J, Kerns KM, Kaufman RJ, Rosen V, Cox KA, Wozney JM (1996) Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo. Growth Factors 13(3–4):291–300

    Article  CAS  PubMed  Google Scholar 

  72. Valera E, Isaacs MJ, Kawakami Y, Izpisúa Belmonte JC, Choe S (2010) BMP-2/6 heterodimer is more effective than BMP-2 or BMP-6 homodimers as inductor of differentiation of human embryonic stem cells. PLoS One 5(6):e11167

    Article  PubMed Central  PubMed  Google Scholar 

  73. Zhu W, Rawlins BA, Boachie-Adjei O, Myers ER, Arimizu J, Choi E, Lieberman JR, Crystal RG, Hidaka C (2004) Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model. J Bone Miner Res 19(12):2021–32

    Article  CAS  PubMed  Google Scholar 

  74. Pietrzak WS, Ali SN, Chitturi D, Jacob M, Woodell-May JE (2011) BMP depletion occurs during prolonged acid demineralization of bone: characterization and implications for graft preparation. Cell Tissue Bank 12(2):81–8

    Article  CAS  PubMed  Google Scholar 

  75. Figueiredo M, Cunhaa S, Martinsa G, Freitasb J, Judasb F, Figueiredoc H (2011) Influence of hydrochloric acid concentration on the demineralization of cortical bone. Chem Eng Res Des 89(1):116–24

    Article  CAS  Google Scholar 

  76. Turonis JW, McPherson JC 3rd, Cuenin MF, Hokett SD, Peacock ME, Sharawy M (2006) The effect of residual calcium in decalcified freeze-dried bone allograft in a critical-sized defect in the Rattus norvegicus calvarium. J Oral Implantol 32(2):55–62

    Article  PubMed  Google Scholar 

  77. Han B, Yang Z, Nimni M (2005) Effects of moisture and temperature on the osteoinductivity of demineralized bone matrix. J Orthop Res 23(4):855–61

    Article  PubMed  Google Scholar 

  78. Nataraj C, Silveira E, Clark J, Yonchek J, Kirk J (2008) Effect of terminal gamma sterilization on osteoinductivity. Report, RTI Biologics, Inc. https://www.exac.com/products/dental-biologics/dental-download-library/design-rationales/effect-of-terminal-gamma-sterilization-on-osteoinductivity. Accessed 12 September 2014

  79. Dziedzic-Goclawska A, Kaminski A, Uhrynowska-Tyszkiewicz I, Stachowicz W (2005) Irradiation as a safety procedure in tissue banking. Cell Tissue Bank 6(3):201–19

    Article  CAS  PubMed  Google Scholar 

  80. Nguyen H, Morgan DA, Forwood MR (2007) Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation? Cell Tissue Bank 8(2):81–91

    Article  PubMed  Google Scholar 

  81. Nguyen H, Morgan DA, Forwood MR (2007) Sterilization of allograft bone: effects of gamma irradiation on allograft biology and biomechanics. Cell Tissue Bank 8(2):93–105

    Article  PubMed  Google Scholar 

  82. Choi J, Sung NY, Lee HS, Kim JH, Byun MW, Woon J (2008) Comparison of electron beam and gamma irradiation for the sterilization of allograft. World Congress on tissue banking, Kuala Lumpur, Malaysia, Ref number 40097233, p 1

  83. Meleady P, Henry M, Gammell P, Doolan P, Sinacore M, Melville M, Francullo L, Leonard M, Charlebois T, Clynes M (2008) Proteomic profiling of CHO cells with enhanced rhBMP-2 productivity following co-expression of PACEsol. Proteomics 8(13):2611–24

    Article  CAS  PubMed  Google Scholar 

  84. Hollinger JO, Mark DE, Goco P, Quigley N, Desverreaux RW, Bach DE (1991) A comparison of four particulate bone derivatives. Clin Orthop Relat Res 267:255–63

    PubMed  Google Scholar 

  85. Peel SA, Hu ZM, Clokie CM (2003) In search of the ideal bone morphogenetic protein delivery system: in vitro studies on demineralized bone matrix, purified, and recombinant bone morphogenetic protein. J Craniofac Surg 14(3):284–91

    Article  PubMed  Google Scholar 

  86. Lindholm TS, Gao TJ (1993) Functional carriers for bone morphogenetic proteins. Ann Chir Gynaecol Suppl 207:3–12

    CAS  PubMed  Google Scholar 

  87. Seeherman H, Wozney JM (2005) Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine Growth Factor Rev 16(3):329–45

    Article  CAS  PubMed  Google Scholar 

  88. Bessa P, Casal M, Reis R (2008) Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J Tissue Eng Regen Med 2(2–3):81–96

    Article  CAS  PubMed  Google Scholar 

  89. Boerckel JD, Kolambkar YM, Dupont KM, Uhrig BA, Phelps EA, Stevens HY, García AJ, Guldberg RE (2011) Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials 32(22):5241–51

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Drossos GI, Kazakos KI, Kouzoumpasis P, Verettas DA (2007) Safety and efficacy of commercially available demineralised bone matrix preparations: a critical review of clinical studies. Injury 38(Suppl 4):S13–21

    Article  Google Scholar 

  91. Hinsenkamp M, Muylle L, Eastlund T, Fehily D, Noël L, Strong DM (2012) Adverse reactions and events related to musculoskeletal allografts: reviewed by the World Health Organisation Project NOTIFY. Int Orthop 36(3):633–41

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Ahn DK, Moon SH, Kim TW, Boo KH, Hong SW (2014) Demineralized bone matrix, as a graft enhancer of auto-local bone in posterior lumbar interbody fusion. Asian Spine J 8(2):129–37

    Article  PubMed Central  PubMed  Google Scholar 

  93. Dumic-Cule I, Brkljacic J, Rogic D, Bordukalo Niksic T, Tikvica Luetic A, Draca N, Kufner V, Trkulja V, Grgurevic L, Vukicevic S (2014) Systemically available bone morphogenetic protein two and seven affect bone metabolism. Int Orthop 38:1979–85

    Article  PubMed  Google Scholar 

  94. NASS North American Spine Society (2014) Recombinant human bone morphogenic protein (rhBMP-2) https://www.spine.org/Documents/PolicyPractice/CoverageRecommendations/rhBMP.pdf. Accessed 12 September 2014

  95. Zhu W, Kim J, Cheng C, Rawlins BA, Boachie-Adjei O, Crystal RG, Hidaka C (2006) Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro. Bone 39(1):61–71

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Rosen V (2006) BMP and BMP inhibitors in bone. Ann NY Acad Sci 1068:19–25

    Article  CAS  PubMed  Google Scholar 

  97. Song K, Krause C, Shi S, Patterson M, Suto R, Grgurevic L, Vukicevic S, van Dinther M, Falb D, Ten Dijke P, Alaoui-Ismaili MH (2010) Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity. J Biol Chem 285(16):12169–80

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Behnam K, Brochmann E, Murray S (2004) Alkali-urea extraction of demineralized bone matrix removes noggin, an inhibitor of bone morphogenetic proteins. Connect Tissue Res 45(4–5):257–60

    Article  CAS  PubMed  Google Scholar 

  99. Kloen P, Lauzier D, Hamdy RC (2012) Co-expression of BMPs and BMP-inhibitors in human fractures and non-unions. Bone 51(1):59–68

    Article  CAS  PubMed  Google Scholar 

  100. Kwong FN, Hoyland JA, Freemont AJ, Evans CH (2009) Altered relative expression of BMPs and BMP inhibitors in cartilaginous areas of human fractures progressing towards nonunion. J Orthop Res 27(6):752–7

    Article  CAS  PubMed  Google Scholar 

  101. Bae H, Zhao L, Zhu D, Kanim LE, Wang JC, Delamarter RB (2010) Variability across ten production lots of a single demineralized bone matrix product. J Bone Joint Surg Am 92(2):427–35

    Article  PubMed  Google Scholar 

  102. Acarturk TO, Hollinger JO (2006) Commercially available demineralized bone matrix compositions to regenerate calvarial critical-sized bone defects. Plast Reconstr Surg 118(4):862–73

    Article  CAS  PubMed  Google Scholar 

  103. Wang JC, Alanay A, Mark D, Kanim LE, Campbell PA, Dawson EG, Lieberman JR (2007) A comparison of commercially available demineralized bone matrix for spinal fusion. Eur Spine J 16(8):1233–40

    Article  PubMed Central  PubMed  Google Scholar 

  104. Bostrom MP, Yang X, Kennan M, Sandhu H, Dicarlo E, Lane JM (2001) An unexpected outcome during testing of commercially available demineralized bone graft materials: how safe are the nonallograft components? Spine 26(13):1425–8

    Article  CAS  PubMed  Google Scholar 

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Author’s disclosure

Maurice Hinsenkamp is Honorary Medical Director of the nonprofit Tissue Bank (BTE) from the Hôpital Erasme at Université Libre de Bruxelles.

Jean-Francois Collard is Technical Director of BTE.

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Correspondence to Maurice Hinsenkamp.

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Hinsenkamp, M., Collard, JF. Growth factors in orthopaedic surgery: demineralized bone matrix versus recombinant bone morphogenetic proteins. International Orthopaedics (SICOT) 39, 137–147 (2015). https://doi.org/10.1007/s00264-014-2562-0

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  • DOI: https://doi.org/10.1007/s00264-014-2562-0

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