Skip to main content
SpringerLink
Log in

Osteogrow: A Novel Bone Graft Substitute for Orthopedic Reconstruction

  • Chapter
  • First Online:
Bone Morphogenetic Proteins: Systems Biology Regulators

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

Complications associated with the clinical use of BMP2 and BMP7 result from the limited understanding of their molecular mechanisms in bone remodeling. Recently, a novel BMP6-based approach has been developed with superior healing results and reduced side effects in preclinical studies. BMP6-containing osteogenic medicinal product called Osteogrow, which is aimed to induce and accelerate bone formation, is currently being tested in clinical studies. It comprises of a biologically compatible autologous carrier made from the patient’s peripheral blood and of rhBMP6 as an active ingredient. Such formulation circumvents the use of animal-derived materials, significantly limits inflammatory processes common in commercial bone devices, and renders the carrier flexible and injectable ensuring the ease of use. The ongoing clinical trial results will provide a more detailed insight into the safety, tolerability, pharmacokinetics, and bone healing effects in humans and hopefully provide novel and valuable therapeutic options in the field of bone regeneration.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. American Academy of Orthopaedic Surgeons (2000) Musculoskeletal injuries report: incidence, risk factors and prevention. AAOS, Rosemont, IL

    Google Scholar 

  2. Andriopoulos B Jr, Corradini E, Xia Y, Faasse SA, Chen S, Grgurevic L, Knutson MD, Pietrangelo A, Vukicevic S, Lin HY, Babitt JL (2009) BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet 41:482–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Axelrad TW, Steen B, Lowenberg DW, Creevy WR, Einhorn TA (2008) Heterotopic ossification after the use of commercially available recombinant human bone morphogenetic proteins in four patients. J Bone Joint Surg Br 90:1617–1622

    Article  CAS  PubMed  Google Scholar 

  4. Bilic R, Simic P, Jelic M, Stern-Padovan R, Dodig D, van Meerdervoort HP, Martinovic S, Ivankovic D, Pecina M, Vukicevic S (2006) Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis. Int Orthop 30:128–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bishop GB, Einhorn TA (2007) Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery. Int Orthop 31:721–727

    Article  PubMed  PubMed Central  Google Scholar 

  6. Boden SD, Zdeblick TA, Sandhu HS, Heim SE (2000) The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report. Spine 25:376–381. Phila Pa 1976

    Google Scholar 

  7. Bong MR, Capla EL, Egol KA, Sorkin AT, Distefano M, Buckle R, Chandler RW, Koval KJ (2005) Osteogenic protein-1 (bone morphogenic protein-7) combined with various adjuncts in the treatment of humeral diaphyseal nonunions. Bull Hosp Jt Dis 63:20–23

    PubMed  Google Scholar 

  8. Bosukonda D, Shih MS, Sampath KT, Vukicevic S (2000) Characterization of receptors for osteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7) in rat kidneys. Kidney Int 58:1902–1911

    Article  CAS  PubMed  Google Scholar 

  9. Carragee EJ, Hurwitz EL, Weiner BK (2011a) A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 11:471–491

    Article  PubMed  Google Scholar 

  10. Carragee EJ, Mitsunaga KA, Hurwitz EL, Scuderi GJ (2011b) Retrograde ejaculation after anterior lumbar interbody fusion using rhBMP-2: a cohort controlled study. Spine J 11:511–516

    Article  PubMed  Google Scholar 

  11. Chatzinikolaidou M, Lichtinger TK, MĂ¼ller RT, Jennissen HP (2010) Peri-implant reactivity and osteoinductive potential of immobilized rhBMP-2 on titanium carriers. Acta Biomater 6:4405–4421

    Article  CAS  PubMed  Google Scholar 

  12. Crawford CH 3rd, Seligson D (2009) Atrophic nonunion of humeral diaphysis treated withlocking plate and recombinant bone morphogenetic protein: nine cases. Am J Orthop (Belle Mead NJ) 38:567–570

    Google Scholar 

  13. 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 38:1979–1985

    Article  PubMed  Google Scholar 

  14. Dumic-Cule I, Pecina M, Jelic M, Jankolija M, Popek I, Grgurevic L, Vukicevic S (2015) Biological aspects of segmental bone defects management. Int Orthop 39:1005–1011

    Article  PubMed  Google Scholar 

  15. Einhorn TA (1995) Enhancement of fracture-healing. J Bone Joint Surg Am 77:940–956

    Article  CAS  PubMed  Google Scholar 

  16. Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res 355 Suppl:S7–21

    Article  Google Scholar 

  17. Einhorn TA, Majeska RJ, Rush EB, Levine PM, Horowitz MC (1995) The expression of cytokine activity by fracture callus. J Bone Miner Res 10:1272–1281

    Article  CAS  PubMed  Google Scholar 

  18. Ekrol I, Hajducka C, Court-Brown C, McQueen MM (2008) A comparison of rhBMP-7 (OP-1) and autogenous graft for metaphyseal defects after osteotomy of the distal radius. Injury 39(Suppl 2):S73–S82

    Article  PubMed  Google Scholar 

  19. 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 158:890–902

    Article  PubMed  Google Scholar 

  20. Giannoudis PV, Kanakaris NK, Einhorn TA (2007) Interaction of bone morphogenetic proteins with cells of the osteoclast lineage: review of the existing evidence. Osteoporos Int 18:1565–1581

    Article  CAS  PubMed  Google Scholar 

  21. Giannoudis PV, Kanakaris NK, Dimitriou R, Gill I, Kolimarala V, Montgomery RJ (2009) The synergistic effect of autograft and BMP-7 in the treatment of atrophic nonunions. Clin Orthop Relat Res 467:3239–3248

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hansen SM, Sasso RC (2006) Resorptive response of rhBMP2 simulating infection in an anterior lumbar interbody fusion with a femoral ring. J Spinal Disord Tech 19:130–134

    Article  PubMed  Google Scholar 

  23. Herrera B, Inman GJ (2009) A rapid and sensitive bioassay for the simultaneous measurement of multiple bone morphogenetic proteins. Identification and quantification of BMP4, BMP6 and BMP9 in bovine and human serum. BMC Cell Biol 10:20

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hiremath GK, Steinmetz MP, Krishnaney AA (2009) Is it safe to use recombinant human bone morphogenetic protein in posterior cervical fusion? Spine 34:885–889. Phila Pa 1976

    Google Scholar 

  25. Hustedt JW, Blizzard DJ (2014) The controversy surrounding bone morphogenetic proteins in the spine: a review of current research. Yale J Biol Med 87:549–561

    PubMed  PubMed Central  Google Scholar 

  26. Kang JD (2011) Another complication associated with rhBMP-2? Spine J 11:517–519

    Article  PubMed  Google Scholar 

  27. Kenley RA, Yim K, Abrams J, Ron E, Turek T, Marden LJ, Hollinger JO (1993) Biotechnology and bone graft substitutes. Pharm Res 10:1393–1401

    Article  CAS  PubMed  Google Scholar 

  28. Kleeman TJ, Ahn UM, Talbot-Kleeman A (2001) Laparoscopic anterior lumbar interbody fusion with rhBMP-2: a prospective study of clinical and radiographic outcomes. Spine 26:2751–2756. Phila Pa 1976

    Google Scholar 

  29. Laursen M, Høy K, Hansen ES, Gelineck J, Christensen FB, BĂ¼nger CE (1999) Recombinant bone morphogenetic protein-7 as an intracorporal bone growth stimulator in unstable thoracolumbar burst fractures in humans: preliminary results. Eur Spine J 8:485–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lavery K, Swain P, Falb D, Alaoui-Ismaili MH (2008) BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J Biol Chem 283:20948–20958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Maric I, Poljak L, Zoricic S, Bobinac D, Bosukonda D, Sampath KT, Vukicevic S (2003) Bone morphogenetic protein-7 reduces the severity of colon tissue damage and accelerates the healing of inflammatory bowel disease in rats. J Cell Physiol 196:258–264

    Article  CAS  PubMed  Google Scholar 

  32. McGee MA, Findlay DM, Howie DW, Carbone A, Ward P, Stamenkov R, Page TT, Bruce WJ, Wildenauer CI, Toth C (2004) The use of OP-1 in femoral impaction grafting in a sheep model. J Orthop Res 22:1008–1015

    Article  CAS  PubMed  Google Scholar 

  33. Mroz TE, Wang JC, Hashimoto R, Norvell DC (2010) Complications related to osteobiologics use in spine surgery: a systematic review. Spine 35:S86–S104. Phila Pa 1976

    Google Scholar 

  34. Notices from European Union Institutions Bodies Offices and Agencies (2011) Note for guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products (EMA/410/01 rev.3). Official Journal of the European Union (2011/C 73/01)

    Google Scholar 

  35. Pauk M, Grgurevic L, Brkljacic J, Kufner V, Bordukalo-Niksic T, Grabusic K, Razdorov G, Rogic D, Zuvic M, Oppermann H, Babitt JL, Lin HY, Volarevic S, Vukicevic S (2015) Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6−/− mice. Int Orthop 39:161–172

    Article  PubMed  Google Scholar 

  36. Pecina M, Vukicevic S (2007) Biological aspects of bone, cartilage and tendon regeneration. Int Orthop 31:719–720

    Article  PubMed  PubMed Central  Google Scholar 

  37. Pecina M, Vukicevic S (2014) Tissue engineering and regenerative orthopaedics (TERO). Int Orthop 38:1757–1760

    Article  PubMed  Google Scholar 

  38. Pecina M, Giltaij LR, Vukicevic S (2001) Orthopaedic applications of osteogenic protein-1 (BMP-7). Int Orthop 25:203–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pradhan BB, Bae HW, Dawson EG, Patel VV, Delamarter RB (2006) Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976) 31:E277–E284

    Article  Google Scholar 

  40. Simmonds MC, Brown JV, Heirs MK, Higgins JP, Mannion RJ, Rodgers MA, Stewart LA (2013) Safety and effectiveness of recombinant human bonemorphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data. Ann Intern Med 158:877–889

    Article  PubMed  Google Scholar 

  41. Song K, Krause C, Shi S, Patterson M, Suto R, Grgurevic L, Vukicevic S, van Dinther M, Falb D, Ten Dijke P (2010) 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 285:12169–12180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vukicevic S, Sampath TK (2002) Bone morphogenetic proteins: from laboratory to clinical practice. Birkhauser Verlag, Basel/Boston/Berlin

    Book  Google Scholar 

  43. Vukicevic S, Sampath TK (2004) Bone morphogenetic proteins: regeneration of bone and beyond. Birkhauser Verlag, Basel/Boston/Berlin

    Book  Google Scholar 

  44. Vukicevic S, Sampath TK (2008) Bone morphogenetic proteins: from local to systemic therapeutics. Birkauser Verlag AG, Basel/Boston/Berlin

    Book  Google Scholar 

  45. Vukicevic S, Basic V, Rogic D, Basic N, Shih MS, Shepard A, Jin D, Dattatreyamurty B, Jones W, Dorai H, Ryan S, Griffiths D, Maliakal J, Jelic M, Pastorcic M, Stavljenic A, Sampath TK (1998) Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat. J Clin Invest 102:202–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Vukicevic S, Grgurevic L, Oppermann H (2012) Whole blood-derived coagulum device for treating bone defects – US Patent 8, 197, 840

    Google Scholar 

  47. 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 proteinsrevisited: a novel biocompatible carrier device OSTEOGROW for bone healing. Int Orthop 38:635–647

    Article  PubMed  Google Scholar 

  48. White AP, Vaccaro AR, Hall JA, Whang PG, Friel BC, McKee MD (2007) Clinicalapplications of BMP-7/OP-1 in fractures, nonunions and spinal fusion. Int Orthop 31:735–741

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Zagreb School of Medicine, Center for Translational and Clinical Research, Laboratory for Mineralized Tissues, Salata 11, Zagreb, Croatia

    Lovorka Grgurevic, Igor Erjavec, Ivo Dumic-Cule, Tatjana Bordukalo-Niksic, Martina Pauk & Slobodan Vukicevic

  2. University of Zagreb School of Medicine, Department of Pharmacology, Salata 11, Zagreb, Croatia

    Vladimir Trkulja

  3. University of Zagreb School of Veterinary Medicine, Clinic for Surgery, Orthopedics and Ophthalmology, Heinzelova 55, Zagreb, Croatia

    Drazen Maticic, Marko Pecin & Marija Lipar

  4. University of Zagreb School of Medicine, Center for Translational and Clinical Research, Department for Intercellular Communication, Salata 2, Zagreb, Croatia

    Mihaela Peric

Authors
  1. Lovorka Grgurevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Igor Erjavec
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ivo Dumic-Cule
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tatjana Bordukalo-Niksic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martina Pauk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vladimir Trkulja
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Drazen Maticic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marko Pecin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marija Lipar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mihaela Peric
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Slobodan Vukicevic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lovorka Grgurevic , Mihaela Peric or Slobodan Vukicevic .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Zagreb, Zagreb, Croatia

    Slobodan Vukicevic

  2. perForm Biologics Inc, Holliston, Massachusetts, USA

    Kuber T. Sampath

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Grgurevic, L. et al. (2017). Osteogrow: A Novel Bone Graft Substitute for Orthopedic Reconstruction. In: Vukicevic, S., Sampath, K. (eds) Bone Morphogenetic Proteins: Systems Biology Regulators. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-47507-3_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-47507-3_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-47505-9

  • Online ISBN: 978-3-319-47507-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation