After blood, bone is the second most common transplanted tissue,1,2 with an estimated 2.2 million grafting procedures worldwide each year.3 Autologous bone graft is considered by many authors to be the gold standard for bone regeneration;4 however it can be associated with a significant complication rate and patient morbidity. Complication rates have been reported to range from 8.6% to 20.6%.1,5-7
A limitation of autograft is that it may not provide the quantity of graft required for specific clinical applications. Cadaveric allograft has limitations with the risk of disease transmission1,8 limited availability, and denaturing of proteins and osteoinductive factors caused by the sterilization process.8
There is a growing need for commercially available, clinically effective bone graft substitutes in all subspecialties of orthopaedic surgery. This short review will focus on bone graft substitutes for oncology (benign bone tumors), pediatrics (unicameral bone cysts), and hip arthroplasty.
Benign Bone Tumors
Bone graft substitutes, either alone or in combination with biological material, have been reported for the treatment of medium to large metaphyseal defects for benign bone tumors and bone cysts. Siegel et al9 reported on 51 patients with benign bone tumors treated with the combination of beta-tricalcium phosphate and osteoprogenitor cells from bone marrow aspirate. At 6 months postoperatively, all implanted grafts demonstrated radiographic features identical to the surrounding cancellous bone. At 1 year, all patients were asymptomatic. Trabeculation and resorption rates were similar and were not associated with the size of the lesion.
El-Adl et al10 reported on 34 patients with benign bone lesions treated with hydroxyapatite/tricalcium phosphate composite bone graft with autogenous bone marrow aspirate. At 19.9 weeks, 70.6% of patients demonstrated substantial healing, 26.5% demonstrated partial healing, and there was one local recurrence. Thirty-one patients had no pain, and there were no pathologic fractures. The rate of bone healing was directly related to the size of defect after curettage.
Shibuya et al11 reported on 62 patients with benign bone tumors filled with hydroxyapatite and bone graft. At 7.9 years, 81% of patients showed "effective" fill of the defect. Calcium sulphate can be utilized safely in benign metaphyseal bone defects but it has a quicker resorption rate with more inconsistent results.12
Faour et al12 noted that the majority of recent authors have opted for synthetic-based materials alone or in combination with bone marrow aspirate. Biphasic macroporous ceramic bone graft substitutes appear effective in the treatment of benign bone lesions. The addition of osteoprogenitor cells from a bone marrow aspirate may accelerate bone healing. There are no studies demonstrating the superiority of bone graft substitutes over morcellized cadaveric allograft for the filling of benign metaphyseal defects.
Evidence-based guidelines to assist the surgeon in choosing the appropriate graft substitute for a particular clinical application are lacking.
Pediatrics (Unicameral Bone Cysts)
Although there are many approaches to the treatment of pediatric unicameral bone cysts, recent studies have evaluated disruption of the cyst wall and injection of a bone graft substitute.13-17 Thawrani et al13 reported an 85% healing rate in 13 benign bone cysts treated with an endothermic calcium phosphate cement injected percutaneously.
Mik et al14 reported on 55 patients who were treated for unicameral bone cysts with calcium sulfate pellets. At a mean follow-up of 37 months, 80% of patients had a complete or partial response after one treatment. Twenty-percent of patients required a secondary procedure.
Joeris et al15 reported on 23 patients treated with percunateous tricalcium sulpfate. The healing rate was 96%. Another study16 reported on 13 patients treated with calcium phosphate pellets. All defects healed with an average time of 13.4 weeks.
Hou17 reported on several modalities in the treatment of unicameral bone cyst. The highest healing rate (92%) was demonstrated with a multimodal approach including curettage of cyst, ethanol cauterization, ablation of cyst with an impactor, calcium sulfate pellets, and placement of a screw.17
Donaldson and Wright18 commented that the lack of clear patho-etiology has impeded the development of simple bone cyst treatment. Although multimodal treatment is an emerging trend, steroid injection of the cyst is the only evidence-based treatment based on a randomized controlled trial.19
Revision Hip Arthroplasty
A major challenge in revision hip surgery is addressing loss of bone stock on either the femoral or the acetabular side. Loss of bone stock is often treated with autograft or cadaveric allograft, often with impaction grafting techniques.20 There is a paucity of long-term literature on bone graft substitutes in revision hip surgery, with no randomized controlled studies to guide clinical practice.
Studies generally have small numbers enrolled and are too short to evaluate implant survival. A recent systematic review by Beswick et al21 identified seven studies22-28 reporting outcomes for bone graft substitutes as an expander to allograft and six studies29-34 using bone graft substitute exclusively. Calcium phosphate ceramics (including hydroxyapatite and tricalcium phosphate) were utilized in 11 studies22,23,25,27-34 and glass ceramic in two studies.24,26 Studies ranged from 6 to 72 patients and mean follow-up from 1 to 13 years.
Blom et al23 reported a prospective cohort study on 43 consecutive patients undergoing acetabular revision using a biphasic porous ceramic bone substitute with 1:1 mixture of bone chips. At mean follow-up of 24 months, there were no revision or implant failures. McNamara et al35 reported on 50 hips under going acetabular reconstruction with porous hydroxyapatite bone substitute and allograft. At a mean follow-up of 60 months, clinical survival was 100% with evidence of incorporation in 60% of hips.
Aulakh et al22 compared outcomes of morcellized allograft alone and in combinations with solid particulate hydroxyapatite in 65 patients. At 13 years, the authors noted similar long-term prosthesis survival and function. A study of 45 revision acetabular cases using granulate glass ionomer cement with allograft showed loosening of 10 components at a mean of 30 months.24
Non-glass ceramic bone graft substitutes show promise as an alternative to or in addition to cadaveric bone graft. The literature does not support the use of glass ceramic bone substitutes at this time for revision hip arthroplasty.
- Finkemeier C.G. Bone-grafting and bone-graft substitutes. The Journal of bone and joint surgery. American volume. Mar 2002;84-A(3):454-464.
- Van Heest A., Swiontkowski M. Bone-graft substitutes. Lancet. Apr 1999;353 Suppl 1:SI28-29.
- Van der Stok J., Van Lieshout E.M., El-Massoudi Y., Van Kralingen G.H., Patka P. Bone substitutes in the Netherlands - a systematic literature review. Acta biomaterialia. Feb 2011;7(2):739-750.
- Nandi S.K., Roy S., Mukherjee P., Kundu B., De D.K., Basu D. Orthopaedic applications of bone graft & graft substitutes: a review. The Indian journal of medical research. Jul 2010;132:15-30.
- Pollock R., Alcelik I., Bhatia C., et al. Donor site morbidity following iliac crest bone harvesting for cervical fusion: a comparison between minimally invasive and open techniques. European spine journal: official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. Jun 2008;17(6):845-852.
- Summers B.N., Eisenstein S.M. Donor site pain from the ilium. A complication of lumbar spine fusion. The Journal of bone and joint surgery. British volume. Aug 1989;71(4):677-680.
- Seiler J.G., 3rd, Johnson J. Iliac crest autogenous bone grafting: donor site complications. Journal of the Southern Orthopaedic Association. Summer 2000;9(2):91-97.
- Boyce T., Edwards J., Scarborough N. Allograft bone. The influence of processing on safety and performance. The Orthopedic clinics of North America. Oct 1999;30(4):571-581.
- Siegel H.J., Baird R.C., 3rd, Hall J., Lopez-Ben R., Lander P.H. The outcome of composite bone graft substitute used to treat cavitary bone defects. Orthopedics. Aug 2008;31(8):754.
- El-Adl G., Mostafa M.F., Enan A., Ashraf M. Biphasic ceramic bone substitute mixed with autogenous bone marrow in the treatment of cavitary benign bone lesions. Acta orthopaedica Belgica. Feb 2009;75(1):110-118.
- Shibuya K., Kurosawa H., Takeuchi H., Niwa S. The medium-term results of treatment with hydroxyapatite implants. Journal of biomedical materials research. Part B, Applied biomaterials. Nov 2005;75(2):405-413.
- Faour O., Dimitriou R., Cousins C.A., Giannoudis P.V. The use of bone graft substitutes in large cancellous voids: any specific needs? Injury. Sep 2011;42 Suppl 2:S87-90.
- Thawrani D., Thai C.C., Welch R.D., Copley L., Johnston C.E. Successful treatment of unicameral bone cyst by single percutaneous injection of alpha-BSM. Journal of pediatric orthopedics. Jul-Aug 2009;29(5):511-517.
- Mik G., Arkader A, Manteghi A, Dormans JP. Results of a minimally invasive technique for treatment of unicameral bone cysts. Clinical orthopaedics and related research. Nov 2009;467(11):2949-2954.
- Joeris A., Ondrus S., Planka L., Gal P., Slongo T. ChronOS inject in children with benign bone lesions--does it increase the healing rate? European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery = Zeitschrift fur Kinderchirurgie. Jan 2010;20(1):24-28.
- Mirzayan R., Panossian V., Avedian R., Forrester D.M., Menendez L.R. The use of calcium sulfate in the treatment of benign bone lesions. A preliminary report. The Journal of bone and joint surgery. American volume. Mar 2001;83-A(3):355-358.
- Hou H.Y., Wu K., Wang C.T., Chang S.M., Lin W.H., Yang R.S. Treatment of unicameral bone cyst: a comparative study of selected techniques. The Journal of bone and joint surgery. American volume. Apr 2010;92(4):855-862.
- Donaldson S., Wright J.G. Recent developments in treatment for simple bone cysts. Current opinion in pediatrics. Feb 2011;23(1):73-77.
- Wright J.G., Yandow S., Donaldson S., Marley L. A randomized clinical trial comparing intralesional bone marrow and steroid injections for simple bone cysts. The Journal of bone and joint surgery. American volume. Apr 2008;90(4):722-730.
- Slooff T.J., Buma P., Schreurs B.W., Schimmel J.W., Huiskes R., Gardeniers J. Acetabular and femoral reconstruction with impacted graft and cement. Clinical orthopaedics and related research. Mar 1996(324):108-115.
- Beswick A., Blom A.W. Bone graft substitutes in hip revision surgery: a comprehensive overview. Injury. Sep 2011;42 Suppl 2:S40-46.
- Aulakh T.S., Jayasekera N., Kuiper J.H., Richardson J.B. Long-term clinical outcomes following the use of synthetic hydroxyapatite and bone graft in impaction in revision hip arthroplasty. Biomaterials. Mar 2009;30(9):1732-1738.
- Blom A.W., Wylde V., Livesey C., et al. Impaction bone grafting of the acetabulum at hip revision using a mix of bone chips and a biphasic porous ceramic bone graft substitute. Acta orthopaedica. Apr 2009;80(2):150-154.
- Engelbrecht E., von Foerster G., Delling G. Ionogran in revision arthroplasty. The Journal of bone and joint surgery. British volume. Mar 2000;82(2):192-199.
- Fujishiro T., Nishikawa T., Takahiro N., et al. Histologic analysis of allograft mixed with hydroxyapatite-tricalcium phosphate used in revision femoral impaction bone grafting. Orthopedics. Mar 2008;31(3):277.
- Kawanabe K., Iida H., Matsusue Y., Nishimatsu H., Kasai R., Nakamura T. A-W glass ceramic as a bone substitute in cemented hip arthroplasty: 15 hips followed 2-10 years. Acta orthopaedica Scandinavica. Jun 1998;69(3):237-242.
- McNamara I.R. Impaction bone grafting in revision hip surgery: past, present and future. Cell and tissue banking. Feb 2010;11(1):57-73.
- Muller M., Stangl R. Norian SRS augmentation in revision of acetabular cup of total hip arthroplasty. A follow up of six patients. Der Unfallchirurg. Apr 2006;109(4):335-338.
- Egawa H., Ho H., Huynh C., Hopper R.H., Jr., Engh C.A,. Jr., Engh C.A. A three-dimensional method for evaluating changes in acetabular osteolytic lesions in response to treatment. Clinical orthopaedics and related research. Feb 2010;468(2):480-490.
- Nich C., Sedel L. Bone substitution in revision hip replacement. International orthopaedics. Dec 2006;30(6):525-531.
- Nishii T., Sugano N., Miki H., Koyama T., Yoshikawa H. Multidetector-CT evaluation of bone substitutes remodeling after revision hip surgery. Clinical orthopaedics and related research. Jan 2006;442:158-164.
- Oonishi H., Iwaki Y., Kin N., et al. Hydroxyapatite in revision of total hip replacements with massive acetabular defects: 4- to 10-year clinical results. The Journal of bone and joint surgery. British volume. Jan 1997;79(1):87-92.
- Wasielewski R.C., Sheridan K.C., Lubbers M.A. Coralline hydroxyapatite in complex acetabular reconstruction. Orthopedics. Apr 2008;31(4):367.
- Schwartz C., Liss P., Jacquemaire B., Lecestre P., Frayssinet P. Biphasic synthetic bone substitute use in orthopaedic and trauma surgery: clinical, radiological and histological results. Journal of materials science. Materials in medicine. Dec 1999;10(12):821-825.
- McNamara I., Deshpande S., Porteous M. Impaction grafting of the acetabulum with a mixture of frozen, ground irradiated bone graft and porous synthetic bone substitute (Apapore 60). The Journal of bone and joint surgery. British volume. May 2010;92(5):617-623.
Reprinted with permission from the Winter 2011 issue of COA Bulletin