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Osteogenic Protein-1 Delivered by Hydroxyapatite-coated Implants Improves Bone Ingrowth in Extracortical Bone Bridging

  • Basic Research
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Extracortical bone bridging for treatment of massive bone loss can improve stability and longevity of massive endoprostheses. Osteogenic protein-1 (OP-1), when used with allograft bone, reportedly improves extracortical bone bridging and bone ingrowth.

Questions/purposes

We asked whether OP-1 delivered by hydroxyapatite (HA) without bone grafting could improve bone ingrowth and bone formation in the context of extracortical bone bridging.

Methods

We implanted unilateral segmental femoral diaphyseal replacement prostheses in 18 dogs (three groups of six dogs). The groups consisted of an HA-coated group augmented with OP-1, an HA-coated group, and a plain porous group. Bone grafting techniques were not used to augment bone formation. The implants were retrieved at 12 weeks for histologic assessment.

Results

After removing one specimen owing to a complication, 17 femora were analyzed (six HA-coated augmented with OP-1, five HA-coated, and six plain). We observed better bone ingrowth in the HA-coated OP-1 group than in the plain porous and HA-coated groups, with no difference between the latter two groups. There also was better bone apposition and callus height in the HA-coated OP-1 group than in the plain group but no differences between the HA-coated OP-1 and HA-coated groups or between the HA-coated and plain groups.

Conclusions

OP-1 (2.9 mg) delivered by HA-coated segmental replacement prostheses in this canine extracortical bone bridging model revealed improved bone ingrowth over HA-coated implants without OP-1 or plain porous-coated prostheses.

Clinical Relevance

OP-1 may be useful as an adjunct to prosthetic reconstruction of massive bone loss without the need for complex bone grafting techniques.

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References

  1. Aebli N, Stich H, Schawalder P, Theis JC, Krebs J. Effects of bone morphogenetic protein-2 and hyaluronic acid on the osseointegration of hydroxyapatite-coated implants: an experimental study in sheep. J Biomed Mater Res A. 2005;73:295–302.

    PubMed  Google Scholar 

  2. Barrack RL, Cook SD, Patron LP, Salkeld SL, Szuszczewicz E, Whitecloud TS III. Induction of bone ingrowth from acetabular defects to a porous surface with OP-1. Clin Orthop Relat Res. 2003;417:41–49.

    PubMed  Google Scholar 

  3. Blunn GW, Briggs TW, Cannon SR, Walker PS, Unwin PS, Culligan S, Cobb JP. Cementless fixation for primary segmental bone tumor endoprostheses. Clin Orthop Relat Res. 2000;372:223–230.

    Article  PubMed  Google Scholar 

  4. Bragdon CR, Doherty AM, Rubash HE, Jasty M, Li XJ, Seeherman H, Harris WH. The efficacy of BMP-2 to induce bone ingrowth in a total hip replacement model. Clin Orthop Relat Res. 2003;417:50–61.

    PubMed  Google Scholar 

  5. Chao EY, Fuchs B, Rowland CM, Ilstrup DM, Pritchard DJ, Sim FH. Long-term results of segmental prosthesis fixation by extracortical bone-bridging and ingrowth. J Bone Joint Surg Am. 2004;86:948–955.

    PubMed  Google Scholar 

  6. Chao EY, Sim FH. Modular prosthetic system for segmental bone and joint replacement after tumor resection. Orthopedics. 1985;8:641–651.

    PubMed  CAS  Google Scholar 

  7. Chao EY, Sim FH. Composite fixation of segmental bone/joint defect replacement (SDR) prostheses: biological and biomechanical justifications. Chir Organi Mov. 1990;75(1 suppl):171–173.

    PubMed  CAS  Google Scholar 

  8. Chao EY, Sim FH. Composite fixation of salvage prostheses for the hip and knee. Clin Orthop Relat Res. 1992;276:91–101.

    PubMed  Google Scholar 

  9. Coathup MJ, Blunn GW, Flynn N, Williams C, Thomas NP. A comparison of bone remodelling around hydroxyapatite-coated, porous-coated and grit-blasted hip replacements retrieved at post-mortem. J Bone Joint Surg Br. 2001;83:118–123.

    Article  PubMed  CAS  Google Scholar 

  10. Cole BJ, Bostrom MP, Pritchard TL, Sumner DR, Tomin E, Lane JM, Weiland AJ. Use of bone morphogenetic protein 2 on ectopic porous coated implants in the rat. Clin Orthop Relat Res. 1997;345:219–228.

    Article  PubMed  Google Scholar 

  11. Cook SD, Baffes GC, Wolfe MW, Sampath TK, Rueger DC. Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model. Clin Orthop Relat Res. 1994;301:302–312.

    PubMed  Google Scholar 

  12. Cook SD, Baffes GC, Wolfe MW, Sampath TK, Rueger DC, Whitecloud TS 3rd. The effect of recombinant human osteogenic protein-1 on healing of large segmental bone defects. J Bone Joint Surg Am. 1994;76:827–838.

    PubMed  CAS  Google Scholar 

  13. Cook SD, Salkeld SL, Patron LP. Bone defect healing with an osteogenic protein-1 device combined with carboxymethylcellulose. J Biomed Mater Res B Appl Biomater. 2005;75:137–145.

    PubMed  Google Scholar 

  14. Cook SD, Thomas KA, Dalton JE, Volkman TK, Whitecloud TS 3rd, Kay JF. Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength. J Biomed Mater Res. 1992;26:989–1001.

    Article  PubMed  CAS  Google Scholar 

  15. Cook SD, Wolfe MW, Salkeld SL, Rueger DC. Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates. J Bone Joint Surg Am. 1995;77:734–750.

    PubMed  CAS  Google Scholar 

  16. Croteau S, Rauch F, Silvestri A, Hamdy RC. Bone morphogenetic proteins in orthopedics: from basic science to clinical practice. Orthopedics. 1999;22:686–695; quiz 696–697.

    PubMed  CAS  Google Scholar 

  17. Fukuroku J, Inoue N, Rafiee B, Sim FH, Frassica FJ, Chao EY. Extracortical bone-bridging fixation with use of cortical allograft and recombinant human osteogenic protein-1. J Bone Joint Surg Am. 2007;89:1486–1496.

    Article  PubMed  Google Scholar 

  18. Geesink RG. Hydroxyapatite-coated total hip prostheses: two-year clinical and roentgenographic results of 100 cases. Clin Orthop Relat Res. 1990;261:39–58.

    PubMed  Google Scholar 

  19. Geesink RG, de Groot K, Klein CP. Chemical implant fixation using hydroxyl-apatite coatings: the development of a human total hip prosthesis for chemical fixation to bone using hydroxyl-apatite coatings on titanium substrates. Clin Orthop Relat Res. 1987;225:147–170.

    PubMed  CAS  Google Scholar 

  20. Geesink RG, de Groot K, Klein CP. Bonding of bone to apatite-coated implants. J Bone Joint Surg Br. 1988;70:17–22.

    PubMed  CAS  Google Scholar 

  21. Gosheger G, Gebert C, Ahrens H, Streitbuerger A, Winkelmann W, Hardes J. Endoprosthetic reconstruction in 250 patients with sarcoma. Clin Orthop Relat Res. 2006;450:164–171.

    Article  PubMed  Google Scholar 

  22. Griffin AM, Parsons JA, Davis AM, Bell RS, Wunder JS. Uncemented tumor endoprostheses at the knee: root causes of failure. Clin Orthop Relat Res. 2005;438:71–79.

    Article  PubMed  Google Scholar 

  23. Guo W, Ji T, Yang R, Tang X, Yang Y. Endoprosthetic replacement for primary tumours around the knee: experience from Peking University. J Bone Joint Surg Br. 2008;90:1084–1089.

    Article  PubMed  CAS  Google Scholar 

  24. Hacking SA, Tanzer M, Harvey EJ, Krygier JJ, Bobyn JD. Relative contributions of chemistry and topography to the osseointegration of hydroxyapatite coatings. Clin Orthop Relat Res. 2002;405:24–38.

    Article  PubMed  Google Scholar 

  25. Jensen TB, Overgaard S, Lind M, Rahbek O, Bunger C, Soballe K. Osteogenic protein 1 device increases bone formation and bone graft resorption around cementless implants. Acta Orthop Scand. 2002;73:31–39.

    Article  PubMed  Google Scholar 

  26. Jeys LM, Kulkarni A, Grimer RJ, Carter SR, Tillman RM, Abudu A. Endoprosthetic reconstruction for the treatment of musculoskeletal tumors of the appendicular skeleton and pelvis. J Bone Joint Surg Am. 2008;90:1265–1271.

    Article  PubMed  CAS  Google Scholar 

  27. Kawai A, Muschler GF, Lane JM, Otis JC, Healey JH. Prosthetic knee replacement after resection of a malignant tumor of the distal part of the femur: medium to long-term results. J Bone Joint Surg Am. 1998;80:636–647.

    Article  PubMed  CAS  Google Scholar 

  28. Kirker-Head CA, Gerhart TN, Armstrong R, Schelling SH, Carmel LA. Healing bone using recombinant human bone morphogenetic protein 2 and copolymer. Clin Orthop Relat Res. 1998;349:205–217.

    Article  PubMed  Google Scholar 

  29. Kirker-Head CA, Gerhart TN, Schelling SH, Hennig GE, Wang E, Holtrop ME. Long-term healing of bone using recombinant human bone morphogenetic protein 2. Clin Orthop Relat Res. 1995;318:222–230.

    PubMed  Google Scholar 

  30. Lind M, Overgaard S, Jensen TB, Song Y, Goodman SB, Bunger C, Soballe K. Effect of osteogenic protein 1/collagen composite combined with impacted allograft around hydroxyapatite-coated titanium alloy implants is moderate. J Biomed Mater Res. 2001;55:89–95.

    Article  PubMed  CAS  Google Scholar 

  31. Lind M, Overgaard S, Nguyen T, Ongpipattanakul B, Bunger C, Soballe K. Transforming growth factor-beta stimulates bone ongrowth: hydroxyapatite-coated implants studied in dogs. Acta Orthop Scand. 1996;67:611–616.

    Article  PubMed  CAS  Google Scholar 

  32. Lind M, Overgaard S, Ongpipattanakul B, Nguyen T, Bunger C, Soballe K. Transforming growth factor-beta 1 stimulates bone ongrowth to weight-loaded tricalcium phosphate coated implants: an experimental study in dogs. J Bone Joint Surg Br. 1996;78:377–382.

    PubMed  CAS  Google Scholar 

  33. Lind M, Overgaard S, Soballe K, Nguyen T, Ongpipattanakul B, Bunger C. Transforming growth factor-beta 1 enhances bone healing to unloaded tricalcium phosphate coated implants: an experimental study in dogs. J Orthop Res. 1996;14:343–350.

    Article  PubMed  CAS  Google Scholar 

  34. Lind M, Overgaard S, Song Y, Goodman SB, Bunger C, Soballe K. Osteogenic protein 1 device stimulates bone healing to hydroxyapaptite-coated and titanium implants. J Arthroplasty. 2000;15:339–346.

    Article  PubMed  CAS  Google Scholar 

  35. Malawer MM, Chou LB. Prosthetic survival and clinical results with use of large-segment replacements in the treatment of high-grade bone sarcomas. J Bone Joint Surg Am. 1995;77:1154–1165.

    PubMed  CAS  Google Scholar 

  36. Nilsson OS, Urist MR, Dawson EG, Schmalzried TP, Finerman GA. Bone repair induced by bone morphogenetic protein in ulnar defects in dogs. J Bone Joint Surg Br. 1986;68:635–642.

    PubMed  CAS  Google Scholar 

  37. Pluhar GE, Manley PA, Heiner JP, Vanderby R Jr, Seeherman HJ, Markel MD. The effect of recombinant human bone morphogenetic protein-2 on femoral reconstruction with an intercalary allograft in a dog model. J Orthop Res. 2001;19:308–317.

    Article  PubMed  CAS  Google Scholar 

  38. Salkeld SL, Patron LP, Barrack RL, Cook SD. The effect of osteogenic protein-1 on the healing of segmental bone defects treated with autograft or allograft bone. J Bone Joint Surg Am. 2001;83:803–816.

    PubMed  Google Scholar 

  39. Soballe K, Hansen ES, Brockstedt-Rasmussen H, Hjortdal VE, Juhl GI, Pedersen CM, Hvid I, Bunger C. Gap healing enhanced by hydroxyapatite coating in dogs. Clin Orthop Relat Res. 1991;272:300–307.

    PubMed  Google Scholar 

  40. Stevenson S, Cunningham N, Toth J, Davy D, Reddi AH. The effect of osteogenin (a bone morphogenetic protein) on the formation of bone in orthotopic segmental defects in rats. J Bone Joint Surg Am. 1994;76:1676–1687.

    PubMed  CAS  Google Scholar 

  41. Sumner DR, Turner TM, Urban RM, Leven RM, Hawkins M, Nichols EH, McPherson JM, Galante JO. Locally delivered rhTGF-beta2 enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injury. J Orthop Res. 2001;19:85–94.

    Article  PubMed  CAS  Google Scholar 

  42. Sumner DR, Turner TM, Urban RM, Turek T, Seeherman H, Wozney JM. Locally delivered rhBMP-2 enhances bone ingrowth and gap healing in a canine model. J Orthop Res. 2004;22:58–65.

    Article  PubMed  CAS  Google Scholar 

  43. Tanzer M, Turcotte R, Harvey E, Bobyn JD. Extracortical bone bridging in tumor endoprostheses: radiographic and histologic analysis. J Bone Joint Surg Am. 2003;85:2365–2370.

    PubMed  Google Scholar 

  44. Tonino A, Oosterbos C, Rahmy A, Therin M, Doyle C. Hydroxyapatite-coated acetabular components: histological and histomorphometric analysis of six cups retrieved at autopsy between three and seven years after successful implantation. J Bone Joint Surg Am. 2001;83:817–825.

    PubMed  Google Scholar 

  45. Torbert JT, Fox EJ, Hosalkar HS, Ogilvie CM, Lackman RD. Endoprosthetic reconstructions: results of long-term followup of 139 patients. Clin Orthop Relat Res. 2005;438:51–59.

    Article  PubMed  Google Scholar 

  46. Tsukeoka T, Suzuki M, Ohtsuki C, Tsuneizumi Y, Miyagi J, Sugino A, Inoue T, Michihiro R, Moriya H. Enhanced fixation of implants by bone ingrowth to titanium fiber mesh: effect of incorporation of hydroxyapatite powder. J Biomed Mater Res B Appl Biomater. 2005;75:168–176.

    PubMed  Google Scholar 

  47. Virolainen P, Inoue N, Nagao M, Ohnishi I, Frassica F, Chao EY. Autogenous onlay grafting for enhancement of extracortical tissue formation over porous-coated segmental replacement prostheses. J Bone Joint Surg Am. 1999;81:493–499.

    PubMed  CAS  Google Scholar 

  48. Ward WG, Johnston KS, Dorey FJ, Eckardt JJ. Extramedullary porous coating to prevent diaphyseal osteolysis and radiolucent lines around proximal tibial replacements: a preliminary report. J Bone Joint Surg Am. 1993;75:976–987.

    PubMed  CAS  Google Scholar 

  49. Yasko AW, Lane JM, Fellinger EJ, Rosen V, Wozney JM, Wang EA. The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2): a radiographic, histological, and biomechanical study in rats. J Bone Joint Surg Am. 1992;74:659–670.

    PubMed  CAS  Google Scholar 

  50. Zegzula HD, Buck DC, Brekke J, Wozney JM, Hollinger JO. Bone formation with use of rhBMP-2 (recombinant human bone morphogenetic protein-2). J Bone Joint Surg Am. 1997;79:1778–1790.

    PubMed  CAS  Google Scholar 

  51. Zhang R, An Y, Toth CA, Draughn RA, Dimaano NM, Hawkins MV. Osteogenic protein-1 enhances osseointegration of titanium implants coated with peri-apatite in rabbit femoral defect. J Biomed Mater Res B Appl Biomater. 2004;71:408–413.

    Article  PubMed  Google Scholar 

  52. Zhang R, Xu D, Landeryou T, Toth C, Dimaano N, Berry J, Evans J, Hawkins M. Ectopic bone formation using osteogenic protein-1 carried by a solution precipitated hydroxyapatite. J Biomed Mater Res A. 2004;71:412–418.

    Article  PubMed  Google Scholar 

  53. Zitelli JP, Higham P. A novel method for solution deposition of hydroxyapatite on to three dimensionally porous metallic surfaces: Peri-Apatite HA. Mat Res Soc Symp Proc. 2000;599:117–128.

    CAS  Google Scholar 

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Acknowledgments

We thank Thomas Bauer MD, for help with the histopathologic analysis and Marie-Eve Robitaille from our institutional animal laboratory for help with our efforts and in caring for the animals during the research period.

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Authors and Affiliations

  1. Division of Orthopaedic Surgery, McGill University Health Centre, Montreal General Hospital, 1650 Cedar Avenue, Room B5.159.6, Montreal, QC, H3G 1A4, Canada

    Neil Saran MD, FRCSC & Robert E. Turcotte MD, FRCSC

  2. Orthobiologics Group, Stryker Orthopaedics, Mahwah, NJ, USA

    Renwen Zhang MD, PhD

Authors
  1. Neil Saran MD, FRCSC
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  2. Renwen Zhang MD, PhD
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  3. Robert E. Turcotte MD, FRCSC
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Corresponding author

Correspondence to Robert E. Turcotte MD, FRCSC.

Additional information

The institution of the authors (NS, RT) has received funding from Stryker Orthopaedics (Mahwah, NJ) for this study. One or more of the authors (RZ) has received payments or benefits from a commercial entity (Stryker Orthopaedics) related to this work. One or more of the authors (RZ) has stock ownership, equity interest, patent/licensing arrangements and/or royalties from Stryker Orthopaedics that could be construed as related to this manuscript.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at the McGill University Health Centre (animal care, surgery, and necropsy including all radiography) and Stryker Orthopaedics (histologic processing).

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Saran, N., Zhang, R. & Turcotte, R.E. Osteogenic Protein-1 Delivered by Hydroxyapatite-coated Implants Improves Bone Ingrowth in Extracortical Bone Bridging. Clin Orthop Relat Res 469, 1470–1478 (2011). https://doi.org/10.1007/s11999-010-1573-4

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  • DOI: https://doi.org/10.1007/s11999-010-1573-4

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