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Applications of bone graft substitutes in sports medicine, trauma and spine surgery
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
There is a relative paucity of literature supporting the use of bone graft substitutes in sports medicine compared with trauma or spinal surgery. One of the most common bone grafting indications in sports medicine is opening wedge tibial osteotomy. When compared alongside autogenous iliac crest bone graft (AICBG), union of tibial osteotomy took longer and pain persisted longer when ceramic wedges were used. At six months post-operatively, there was no difference between the two groups in terms of union and outcome.1 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 osteotomies.2 It is currently unclear whether there is a need to graft the osteotomy site for corrections of < 10°. 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 (Smith & Nephew), a biphasic polymer scaffold, has been studied as a donor site filler in mosaicplasty.3 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 repair.4 The short-term clinical and radiological outcomes were considered modest, but it has been shown that the grafts tend to mature with time,3 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 anterior cruciate ligament (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 surgery
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 defects.5-8 The injection of calcium phosphate following closed reduction and cast immobilisation of distal radius fracture led to higher patient satisfaction and lower malunion incidence than cast immobilisation alone.6 In tibial plateau and distal radius fractures, injections of calcium phosphate improved the maintenance of articular surface reduction compared with autograft.8 Its use also allowed early weight-bearing without loss of articular surface reduction in calcaneum and tibial plateau fractures,9,10and improved post-operative proximal femoral fracture stability.11 Finally, a recent meta-analysis confirmed that calcium phosphate cement decreased pain, maintained fracture reduction and improved functional outcomes when used in fracture treatment.12
Recombinant human bone morphogenic protein (rhBMP) is reported to be useful in fracture management, decreasing healing time and union rate.13-19
Biological 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.
Spinal surgery
Common applications of bone graft substitutes in spinal surgery include vertebral fusion and fractured vertebral body. The efficacy of injection of polymethylmethacrylate cement (PMMA) into a vertebral body fracture has recently been questioned.20 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 with autogenous iliac crest bone graft,21,22 although neither of these studies describe a rate of fusion. On the other hand, rhBMP has been widely studied in lumbar vertebral fusion procedures. Prospective randomised trials report better outcomes (fusion rate, blood loss, operative time, reoperation rate) with the use of rhBMP-2 compared with autogenous iliac crest graft.23-25 Safety remains a concern, however, with the use of rhBMP in spinal surgery with reports describing complication rates between 10% and 50% depending on the approach (ectopic bone formation in and around the spinal canal, post-operative 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. Gouin F, Yaouanc F, Waast D, et al. Open wedge high tibial osteotomies: calcium-phosphate ceramic spacer versus autologous bonegraft. Orthop Trauma Surg Res 2010;96:637-45.
2. Zorzi AR, da Silva HG, Muszkat C, et al. Opening-wedge high tibial osteotomy with and without bone graft. Artif Organs 2011;35:301-7.
3. Bedi A, Foo LF, Williams RJ, Potter HG; Cartilage Study Group. The maturation of synthetic scaffolds for osteochondral donor sites of the knee: an MRI and T2-mapping analysis. Cartilage 2010;1:20-8.
4. Dhollander AA, Liekens K, Almqvist KF, et al. 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 2012;28:225-33.
5. Jupiter JB, Winters S, Sigman S, et al. Repair of five distal radius fractures with an investigational cancellous bone cement: a preliminary report. J Orthop Trauma 1997;11:110-16.
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] 2000;82-B:856-63.
7. Cassidy C, Jupiter JB, Cohen M, et al. Norian SRS cement compared with conventional fixation in distal radius fractures: a randomized study. J Bone Joint Surg [Am] 2003;85-A:2127-37.
8. Dickson KF, Friedman J, Buchholz JG, Flandry FD. The use of BoneSource hydroxyapatite cement for traumatic metaphyseal bone void filling. J Trauma 2002;53:1103-08.
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 Trauma2002;16:143-9.
10. Schildhauer TA, Bauer TW, 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 2000;14:309-17.
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 2003;92:215-19.
12. Bajammal SS, 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] 2008;90-A:1186-96.
13. Friedlaender GE, Perry CR, Cole JD, et al. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg [Am] 2001;83-A(Suppl 1, Pt 2):S151-8.
14. Govender S, Csimma C, Genant HK, 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] 2002;84-A:2123-34.
15. Swiontkowski MF, Aro HT, 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]2006;88-A:1258-65.
16. Giannoudis PV, Tzioupis C. Clinical applications of BMP-7: the UK perspective. Injury 2005;36(Suppl 3):S47-50.
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 2006;109:528-37.
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 2006;30:128-34.
19. Jones AL, Bucholz RW, Bosse MJ, 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]2006;88-A:1431-41.
20. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009;361:569-79.
21. Fujibayashi S, Shikata J, Tanaka C, Matsushita M, Nakamura T. Lumbar posterolateral fusion with biphasic calcium phosphate ceramic. J Spinal Disord 2001;14:214-21.
22. Lerner T, Bullmann V, Schulte TL, 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 2009;18:170-9.
23. Burkus JK, Gornet MF, Dickman CA, et al. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech 2002;15:337-49.
24. Boden SD, 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 (Phila Pa 1976) 2002;27:2662-73.
25. Dimar JR, Glassman SD, Burkus JK, 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] 2009;91-A:1377-86.
26. Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 2011;11:471-91.
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