Applications of Bone Graft Substitutes in Sports Medicine, Trauma and Spine Surgery

Patrick Lavigne, M.D., PhD, FRCSC
Montreal, QC

Bone graft substitutes are now commonly used in orthopaedic surgery as an alternative to autogenous bone graft. This short review will focus on applications of bone graft substitutes in sports medicine, trauma and spine surgery.

 

Sports Medicine Applications
There is a relative paucity of literature supporting the use of bone graft substitutes in sports medicine in comparison to trauma or spine surgery. One of the most common bone grafting indications in sports medicine is opening wedge tibial osteotomy. When compared to autogenous iliac crest bone graft (AICBG), union of tibial osteotomy took longer and pain persisted longer when ceramic wedges were used. At six months postop, there was no difference between both groups in union and outcome1. Recently, the use of bone grafting in osteotomy has been questioned in a study that showed no difference in complications, union time and rate in grafted and non-grafted osteotomies2. It is currently unclear whether there is a need to graft the osteotomy site for corrections less than 10 degrees. The existing evidence in the literature does not report any advantages of using synthetic wedges in this setting.

Osteochondral defect is another potential application for bone graft substitutes. The TruFit plug, a biphasic polymer scaffold, has been studied as a donor site filler in mosaicplasty3. The author showed good integration of the TruFit plug with mean MRI T2 relaxation times approaching those of normal articular cartilage. The same implant was tested in knee cartilage repair4. The short-term clinical and radiologic outcomes were considered modest, but it has been shown that the grafts tend to mature with time3, suggesting that a longer follow-up period is needed before any conclusions can be drawn.

Other applications for bone graft substitutes in sports medicine include ACL autograft donor sites, graft tunnel expansion in ACL revision surgery and glenoid and humeral head defect in shoulder instability. There is, however, no evidence to support their use in the literature.

Trauma Applications
Bone defect is common after orthopaedic trauma and bone graft substitutes are frequently used in this setting to fill metaphyseal voids. Calcium phosphate has been extensively studied in metaphyseal defects5-8. The injection of calcium phosphate following closed reduction and cast immobilization of distal radius fracture led to higher patient satisfaction and lower malunion incidence than cast immobilization alone6. In tibial plateau and distal radius fractures, calcium phosphate injections improved the maintenance of articular surface reduction compared to autograft8. Its use also allowed early weight-bearing without loss of articular surface reduction in calcaneum and tibial plateau fractures9,10, and improved postoperative proximal femoral fracture stability11. Finally, a recent meta-analysis confirmed that calcium phosphate cement decreased pain, improved maintenance of fracture reduction and functional outcomes when used in fracture treatment12.

Recombinant human bone morphogenic proteins (rhBMP) are reported to be useful in fracture management, decreasing healing time and union rate13-19.

Biologic and systemic factors are also available to improve fracture healing. Most of these factors have insufficient data in preclinical trials to determine efficacy, but platelet-derived growth factor and parathyroid hormone appear promising.

Spine Applications
Common applications of bone graft substitutes in spine surgery include vertebral fusion and fractured vertebral body. The efficacy of injection of polymethylmethacrylate cement (PMMA) into a vertebral body fracture has recently been questioned20. Calcium phosphate and calcium sulfate cement are currently studied as alternative to PMMA but there is not enough evidence to support their use.

In posterolateral spine fusion procedures, bone graft substitutes have been shown to reduce pain and blood loss when compared to autogenous iliac crest bone graft21,22. No reports on fusion rate are described in those studies. On the other hand, rhBMP has been widely studied in lumbar vertebral fusion procedures. Prospective randomized trials report better outcomes (fusion rate, blood loss, operative time, reoperation rate) with the use of rhBMP-2 compared to autogenous iliac crest graft23-25. Safety remains a concern, however, with the use of rhBMP in spine surgery with reports describing 10-50% complication rate depending on the approach (ectopic bone formation in and around the spinal canal, postoperative radiculitis, vertebral osteolysis and allergic/ hyperinflammatory response)26.

Platelet gels, demineralized bone matrix and bone grafts substitute have promising preclinical data but lack sufficient clinical data demonstrating efficacy in lumbar fusion.

References

  1. Gouina F., Yaouanca F., Waasta D., Melchiorc B., Delecrina J., Passutia N. Open wedge high tibial osteotomies: Calcium-phosphate ceramic spacer versus autologous bonegraft. Orthopaedics & Traumatology: Surgery & Research 96, 637-45, 2010.
  2. Zorzi A.R., da Silva H.G., Muszkat C., Marques L.C., Cliquet A., de Miranda J.B. Opening-wedge high tibial osteotomy with and without bone graft. Artif Organs 35(3):301-7, 2011.
  3. Bedi A., Foo L.F., Williams R.J., Potter H.G., and the Cartilage Study Group. The Maturation of Synthetic Scaffolds for Osteochondral Donor Sites of the Knee: An MRI and T2-Mapping Analysis. Cartilage 1 : 20-8, 2010.
  4. Dhollander A.A., Liekens K., Almqvist K.F., Verdonk R., Lambrecht S., Elewaut D., Verbruggen G., Verdonk P.C. A Pilot Study of the Use of an Osteochondral Scaffold Plug for Cartilage Repair in the Knee and How to Deal With Early Clinical Failures. Arthroscopy. 2011 Oct 18. [Epub ahead of print].
  5. Jupiter J.B., Winters S., Sigman S., et al: Repair of five distal radius fractures with an investigational cancellous bone cement: A preliminary report. J Orthop Trauma 11:110-16 1997.
  6. Sanchez-Sotelo J., Munuera L., Madero R.: Treatment of fractures of the distal radius with a remodellable bone cement: A prospective, randomised study using Norian SRS. J Bone Joint Surg Br 82:856-63, 2000.
  7. Cassidy C., Jupiter J.B., Cohen M., et al: Norian SRS cement compared with conventional fixation in distal radius fractures: A randomized study. J Bone Joint Surg Am 85:2127-37, 2003.
  8. Dickson K.F., Friedman J., Bucholz J.G., Flandry F.D.: The use of BoneSource hydroxyapatite cement for traumatic metaphyseal bone void filling. J Trauma 53:1103-08, 2002.
  9. Lobenhoffer P., Gerich T., Witte F., Tscherne H.: Use of injectable calcium phosphate cement in the treatment of tibial plateau fractures: A prospective study of twenty-six cases with twenty- month mean follow-up. J Orthop Trauma16:143-49, 2002.
  10. Schildhauer T.A., Bauer T.W., Josten C., Muhr G.: Open reduction and augmentation of internal fixation with an injectable skeletal cement for the treatment of complex calcaneal fractures. J Orthop Trauma 14:309-17, 2000.
  11. Mattsson P., Larsson S.: Stability of internally fixed femoral neck fractures augmented with resorbable cement: A prospective randomized study using radiostereometry. Scand J Surg 92:215-19, 2003.
  12. Bajammal S.S., Zlowodzki M., Lelwica A., et al. The use of calcium phosphate bone cement in fracture treatment. A meta-analysis of randomized trials. J Bone Joint Surg Am 90:1186-96, 2008.
  13. Friedlaender G.E., Perry C.R., Cole J.D., et al. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am. 83 Suppl 1(Pt 2):S151-8, 2001.
  14. Govender S., Csimma C., Genant H.K., et al. BMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) Study Group. 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 84:2123-34, 2002.
  15. Swiontkowski M.F., Aro H.T., Donell S., et al. Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J Bone Joint Surg Am 88:1258-65, 2006.
  16. Giannoudis P.V., Tzioupis C. Clinical applications of BMP-7: the UK perspective. Injury. 36 Suppl 3:S47-50, 2005.
  17. Zimmermann G., Moghaddam A., Wagner C., Vock B., Wentzensen A. Clinical experience with bone morphogenetic protein 7 (BMP 7) in nonunions of long bones. Unfallchirurg 109:528-37, 2006.
  18. Bilic R., Simic P., Jelic M., et al. Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis. Int Orthop 30:128-34, 2006.
  19. Jones A.L., Bucholz R.W., Bosse M.J., et al. BMP-2 Evaluation in Surgery for Tibial Trauma- Allograft (BESTT-ALL) Study Group. Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial. J Bone Joint Surg Am 88:1431-41, 2006.
  20. Kallmes D.F., Comstock B.A., Heagerty P.J., et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 361(6):569-79, 2009.
  21. Fujibayashi S., Shikata J., Tanaka C., Matsushita M., Nakamura T.: Lumbar posterolateral fusion with biphasic calcium phosphate ceramic. J Spinal Disord 14(3):214-21, 2001.
  22. Lerner T., Bullmann V., Schulte T.L., Schneider M., Liljenqvist U.: A level-1 pilot study to evaluate of ultraporous beta-tricalcium phosphate as a graft extender in the posterior correction of adolescent idiopathic scoliosis. Eur Spine J 18(2):170-79, 2009.
  23. Burkus J.K., Gornet M.F., Dickman C.A., et al. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech 15:337- 49, 2002.
  24. Boden S.D., Kang J., Sandhu H., et al. Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies. Spine 27:2662-73, 2002.
  25. Dimar J.R. II, Glassman S.D., Burkus J.K., et al. Clinical and radiographic analysis of an optimized rhBMP-2 formulation as an autograft replacement in posterolateral lumbar spine arthrodesis. J Bone Joint Surg Am 91: 1377- 86, 2009.
  26. Carragee E.J., Hurwitz E.L., Weiner B.K. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery : emerging safety concerns and lessons learned. Spine J 11 :471-91, 2011.

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