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Calcified Tissue International

, Volume 104, Issue 2, pp 115–129 | Cite as

Efficacy of rhBMP-2 in Cleft Lip and Palate Defects: Systematic Review and Meta-analysis

  • Wellington Luiz de Oliveira da Rosa
  • Tiago Machado da Silva
  • Arthur Dias Galarça
  • Evandro Piva
  • Adriana Fernandes da SilvaEmail author
Review
  • 69 Downloads

Abstract

The aim of this study was to analyze the efficacy of using rhBMP-2 (recombinant human morphogenetic protein-2) in the treatment of patients with cleft lip and palate defects (CLPD). Seven databases were screened: PubMed (Medline), Lilacs, Ibecs, Web of Science, BBO, Scopus, and The Cochrane Library. Clinical trials that evaluated the use of bioactive treatment with rhBMP-2 in the treatment of patients with CLPD were included. Statistical analyses were performed by comparing the standardized mean difference of bone formation volume and bone filling percentage (p = 0.05). Ten studies compared the use of rhBMP-2 and iliac crest bone graft (ICBG). The global analysis for bone formation volume and bone filling percentage showed that bioactive materials were similar to ICBG with a standardized mean difference of respectively 0.07 (95% CI − 0.41 to 0.56) and 0.24 (95% CI − 0.32 to 0.80). The available literature suggested that use of rhBMP-2 presented similar bone formation results to those of ICBG in secondary alveolar bone grafting for patients with CLPD.

Keywords

Bone transplantation Cleft palate Bone morphogenetic protein Review 

Notes

Acknowledgements

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and DOCFIX #88887.195037/2018-00. The present research was also supported by the Fundação de Amparo à Pesquisa do Rio Grande do Sul (Pronex FAPERGS #16.0471-4) and by National Council of Technological and Scientific Development (CNPq - grant Technological Development).

Author Contributions

WLOR, TMS, and AFS designed the study. WLOR and TMS prepared the first draft of the paper. WLOR was responsible for statistical analysis of the data. WLOR, ADG, and EP prepared the final draft of the manuscript. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

Compliance with Ethical Standards

Conflict of interest

Wellington Luiz de Oliveira da Rosa, Tiago Machado da Silva, Arthur Dias Galarça, Evandro Piva, and Adriana Fernandes da Silva have no conflicts of interest related to this work.

Research Involving Human and Animal Participants

There were no human or animal studies conducted by the authors who were described in this review.

Informed consent

The study is with secondary data from other papers. Informed consent was obtained from all individual participants in each included study for whom identifying information is included in this article.

References

  1. 1.
    Pradel W, Tausche E, Gollogly J, Lauer G (2008) Spontaneous tooth eruption after alveolar cleft osteoplasty using tissue-engineered bone: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 105:440–444.  https://doi.org/10.1016/j.tripleo.2007.07.042 CrossRefGoogle Scholar
  2. 2.
    Vecchiatini R, Mobilio N, Raimondi F et al (2009) Implant-prosthetic rehabilitation for a patient with monolateral cleft lip and palate: a clinical report. Quintessence Int 40:445–447Google Scholar
  3. 3.
    Khojasteh A, Behnia H, Naghdi N et al (2013) Effects of different growth factors and carriers on bone regeneration: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol 116:e405–e423.  https://doi.org/10.1016/j.oooo.2012.01.044 CrossRefGoogle Scholar
  4. 4.
    van Hout WMMT, van der Molen ABM, Breugem CC et al (2011) Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2. Clin Oral Invest 15:297–303.  https://doi.org/10.1007/s00784-011-0547-6 CrossRefGoogle Scholar
  5. 5.
    Canan LW, Da Silva Freitas R, Alonso N et al (2012) Human bone morphogenetic protein-2 use for maxillary reconstruction in cleft lip and palate patients. J Craniofac Surg 23:1627–1633.  https://doi.org/10.1097/SCS.0b013e31825c75ba CrossRefGoogle Scholar
  6. 6.
    Gupta C, Mehrotra D, Mohammad S et al (2013) Alveolar bone graft with platelet rich plasma in cleft alveolus. J Oral Biol Craniofac Res 3:3–8.  https://doi.org/10.1016/j.jobcr.2013.02.002 CrossRefGoogle Scholar
  7. 7.
    Francis CS, Mobin SSN, Lypka MA et al (2013) RhBMP-2 with a demineralized bone matrix scaffold versus autologous iliac crest bone graft for alveolar cleft reconstruction. Plast Reconstr Surg 131:1107–1115.  https://doi.org/10.1097/PRS.0b013e3182865dfb CrossRefGoogle Scholar
  8. 8.
    Hibi H, Yamada Y, Ueda M, Endo Y (2006) Alveolar cleft osteoplasty using tissue-engineered osteogenic material. Int J Oral Maxillofac Surg 35:551–555.  https://doi.org/10.1016/j.ijom.2005.12.007 CrossRefGoogle Scholar
  9. 9.
    Behnia H, Khojasteh A, Soleimani M et al (2012) Repair of alveolar cleft defect with mesenchymal stem cells and platelet derived growth factors: a preliminary report. J Cranio-Maxillofac Surg 40:2–7.  https://doi.org/10.1016/j.jcms.2011.02.003 CrossRefGoogle Scholar
  10. 10.
    Janssen NG, Weijs WLJ, Koole R et al (2014) Tissue engineering strategies for alveolar cleft reconstruction: a systematic review of the literature. Clin Oral Invest 18:219–226.  https://doi.org/10.1007/s00784-013-0947-x CrossRefGoogle Scholar
  11. 11.
    Herford AS, Miller M, Signorino F (2017) Maxillofacial defects and the use of growth factors. Oral Maxillofac Surg Clin North Am 29:75–88.  https://doi.org/10.1016/j.coms.2016.08.006 CrossRefGoogle Scholar
  12. 12.
    Janssen NG, Weijs WL, Koole R et al (2014) Tissue engineering strategies for alveolar cleft reconstruction: a systematic review of the literature. Clin Oral Invest 18:219–226.  https://doi.org/10.1007/s00784-013-0947-x CrossRefGoogle Scholar
  13. 13.
    Laurie SW, Kaban LB, Mulliken JB, Murray JE (1984) Donor-site morbidity after harvesting rib and iliac bone. Plast Reconstr Surg 73:933–938.  https://doi.org/10.1097/00006534-198406000-00014 CrossRefGoogle Scholar
  14. 14.
    Dickinson BP, Ashley RK, Wasson KL et al (2008) Reduced morbidity and improved healing with bone morphogenic protein-2 in older patients with alveolar cleft defects. Plast Reconstr Surg 121:209–217CrossRefGoogle Scholar
  15. 15.
    Francis CS, Mobin SSN, Lypka M et al (2013) rhBMP-2 with a demineralized bone matrix scaffold versus autologous iliac crest bone graft for alveolar cleft reconstruction. Plast Reconstr Surg 131:1107–1115.  https://doi.org/10.1097/PRS.0b013e3182865dfb CrossRefGoogle Scholar
  16. 16.
    Alonso N, Risso GH, Denadai R, Raposo-Amaral CE (2014) Effect of maxillary alveolar reconstruction on nasal symmetry of cleft lip and palate patients: a study comparing iliac crest bone graft and recombinant human bone morphogenetic protein-2. J Plast Reconstr Aesthetic Surg 67:1201–1208.  https://doi.org/10.1016/j.bjps.2014.05.014 CrossRefGoogle Scholar
  17. 17.
    Marukawa E, Oshina H, Iino G et al (2011) Reduction of bone resorption by the application of platelet-rich plasma (PRP) in bone grafting of the alveolar cleft. J Cranio-Maxillofac Surg 39:278–283.  https://doi.org/10.1016/j.jcms.2010.04.017 CrossRefGoogle Scholar
  18. 18.
    Sailer HF, Kolb E (1994) Application of purified bone morphogenetic protein (BMP) in cranio-maxillo-facial surgery. BMP in compromised surgical reconstructions using titanium implants. J Cranio-Maxillofac Surg 22:2–11.  https://doi.org/10.1016/S1010-5182(05)80289-6 CrossRefGoogle Scholar
  19. 19.
    Azari K, Doctor JS, Doll BA, Hollinger JO (2002) Bone morphogenetic proteins. A review for cranial and maxillofacial surgery. Oral Maxillofac Surg Clin North Am 14:1–14.  https://doi.org/10.1016/s1042-3699(02)00011-0 CrossRefGoogle Scholar
  20. 20.
    Urist MR, Strates BS (1971) Bone morphogenetic protein. J Dent Res 50:1392CrossRefGoogle Scholar
  21. 21.
    Urist MR (1965) Bone: formation by autoinduction. Science 150:1893CrossRefGoogle Scholar
  22. 22.
    Wozney J (1989) Bone morphogenetic proteins. Prog Growth Factor Res 1:267–280CrossRefGoogle Scholar
  23. 23.
    Balaji SM (2009) Use of recombinant human bone morphogenetic protein (rhBMP-2) in reconstruction of maxillary alveolar clefts. J Maxillofac Oral Surg 8:211–217.  https://doi.org/10.1007/s12663-009-0052-5 CrossRefGoogle Scholar
  24. 24.
    Gomes-Ferreira PHS, Okamoto R, Ferreira S et al (2016) Scientific evidence on the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in oral and maxillofacial surgery. Oral Maxillofac Surg 20:223–232.  https://doi.org/10.1007/s10006-016-0563-4 CrossRefGoogle Scholar
  25. 25.
    da Rosa WL de O, da Silva TM, da Silva AF, Piva E (2017) Bioactive treatments in bone grafts for implant-based rehabilitation: systematic review and meta-analysis. Clin Implant Dent Relat Res 1–10.  https://doi.org/10.1111/cid.12552
  26. 26.
    da Rosa WL, Piva E, Silva AF (2018) Disclosing the physiology of dental pulp for vital pulp therapy. Int Endod J.  https://doi.org/10.1111/iej.12906 Google Scholar
  27. 27.
    Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62:1006–1012.  https://doi.org/10.1016/j.jclinepi.2009.06.005 CrossRefGoogle Scholar
  28. 28.
    Higgins JP, Green S (2008) Cochrane handbook for systematic reviews of interventions: cochrane book series. Wiley: HobokenCrossRefGoogle Scholar
  29. 29.
    da Lima AFM, Rahal SC, dos Volpi RS et al (2007) Effect of bovine bone morphogenetic proteins on radius fracture healing in rabbits. Acta Cir Bras 22:259–264CrossRefGoogle Scholar
  30. 30.
    Clokie CML, Sándor GKB (2008) Reconstruction of 10 major mandibular defects using bioimplants containing BMP-7. J Can Dent Assoc 74:67–72Google Scholar
  31. 31.
    Neovius E, Lemberger M, Docherty Skogh AC et al (2013) Alveolar bone healing accompanied by severe swelling in cleft children treated with bone morphogenetic protein-2 delivered by hydrogel. J Plast Reconstr Aesthet Surg 66:37–42CrossRefGoogle Scholar
  32. 32.
    Hammoudeh JA, Fahradyan A, Gould DJ et al (2017) A comparative analysis of recombinant human bone morphogenetic protein-2 with a demineralized bone matrix versus iliac crest bone graft for secondary alveolar bone grafts in patients with cleft lip and palate: review of 501 cases. Plast Reconstr Surg 140:318–325.  https://doi.org/10.1097/PRS.0000000000003519 CrossRefGoogle Scholar
  33. 33.
    Liang F, Yen SLK, Imahiyerobo T et al (2017) Three-dimensional cone beam computed tomography volumetric outcomes of rhBMP-2/demineralized bone matrix versus iliac crest bone graft for alveolar cleft reconstruction. Plast Reconstr Surg 140:767–774.  https://doi.org/10.1097/PRS.0000000000003686 CrossRefGoogle Scholar
  34. 34.
    Alonso N, Tanikawa DYS, Freitas R da S, et al (2010) Evaluation of maxillary alveolar reconstruction using a resorbable collagen sponge with recombinant human bone morphogenetic protein-2 in cleft lip and palate patients. Tissue Eng C Methods 16:1183–1189.  https://doi.org/10.1089/ten.tec.2009.0824 CrossRefGoogle Scholar
  35. 35.
    Herford AS, Boyne PJ, Rawson R, Williams RP (2007) Bone morphogenetic protein-induced repair of the premaxillary cleft. J Oral Maxillofac Surg 65:2136–2141.  https://doi.org/10.1016/j.joms.2007.06.670 CrossRefGoogle Scholar
  36. 36.
    Zhang H, Sucato DJ, Welch RD (2005) Recombinant human bone morphogenic protein-2-enhanced anterior spine fusion without bone encroachment into the spinal canal: a histomorphometric study in a thoracoscopically instrumented porcine model. Spine 30:512–518.  https://doi.org/10.1097/01.brs.0000154651.62088.e3 CrossRefGoogle Scholar
  37. 37.
    Bessa PC, Casal M, Reis RL (2008) Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J Tissue Eng Regen Med 2:81–96CrossRefGoogle Scholar
  38. 38.
    Bergman K, Engstrand T, Hilborn J et al (2009) Injectable cell-free template for bone-tissue formation. J Biomed Mater Res A 91:1111–1118.  https://doi.org/10.1002/jbm.a.32289 CrossRefGoogle Scholar
  39. 39.
    Cohen M, Figueroa AA, Haviv Y et al (1991) Iliac versus cranial bone for secondary grafting of residual alveolar clefts. Plast Reconstr Surg 87:423–427.  https://doi.org/10.1097/00006534-199103000-00004 CrossRefGoogle Scholar
  40. 40.
    Harsha BC, Turvey TA, Powers SK (1986) Use of autogenous cranial bone grafts in maxillofacial surgery: a preliminary report. J Oral Maxillofac Surg 44:11–15.  https://doi.org/10.1016/0278-2391(86)90008-X CrossRefGoogle Scholar
  41. 41.
    Denny AD, Talisman R, Bonawitz SC (1999) Secondary alveolar bone grafting using milled cranial bone graft: a retrospective study of a consecutive series of 100 patients. Cleft Palate Craniofacial J 36:144–153.  https://doi.org/10.1597/1545-1569 CrossRefGoogle Scholar
  42. 42.
    Shields LBE, Raque GH, Glassman SD et al (2006) Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior. Cervical Spine Fusion 31:542–547Google Scholar
  43. 43.
    Carragee EJ, Hurwitz EL, Weiner BK (2011) 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.  https://doi.org/10.1016/j.spinee.2011.04.023 CrossRefGoogle Scholar
  44. 44.
    Balaji SM (2009) Mandibular cystic defect: a composite approach with rhBMP-2 and rib graft. J Maxillofac Oral Surg 8:27–30.  https://doi.org/10.1007/s12663-009-0007-x CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Wellington Luiz de Oliveira da Rosa
    • 1
  • Tiago Machado da Silva
    • 1
  • Arthur Dias Galarça
    • 1
  • Evandro Piva
    • 1
  • Adriana Fernandes da Silva
    • 1
    • 2
    Email author
  1. 1.Department of Restorative Dentistry, School of DentistryFederal University of PelotasPelotasBrazil
  2. 2.Department of Restorative Dentistry, Faculty of DentistryFederal University of PelotasPelotasBrazil

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