Javascript not enabled
OncologyFocus On...

Bone graft substitutes in oncology, paediatrics, and hip arthroplasty

J. M. Werier

After blood, bone is the second most common transplanted tissue1,2 with an estimated 2.2 million grafting procedures annually worldwide.3 Autologous bone graft is considered by many authors to be the gold standard for bone regeneration4; however, it can be associated with patient morbidity and significant complication rates, ranging 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, including the risk of disease transmission,1,8 limited availability, and denaturing of proteins and osteoinductive factors caused by the sterilisation 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 tumours), paediatrics (unicameral bone cysts), and hip arthroplasty.

Benign tumours of bone and unicameral bone cysts

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 tumours and bone cysts. Siegel et al9 reported on 51 patients with benign bone tumours treated with the combination of beta-tricalcium phosphate and osteoprogenitor cells from bone marrow aspirate. At six months post-operatively, all implanted grafts demonstrated radiological features identical to the surrounding cancellous bone. At one 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. A total of 31 patients had no pain, and there were no pathological 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 tumours filled with hydroxyapatite and bone graft. At 7.9 years 81% of patients showed ‘effective’ fill of defect. Calcium sulphate can be used 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 morcellised 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.


Although there are many approaches to the treatment of paediatric 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 a healing rate of 85% in 13 benign bone cysts treated with an endothermic calcium phosphate cement injected percutaneously.

Mik et al14 described 55 patients who were treated for unicameral bone cysts with calcium sulphate pellets. At a mean follow-up of 37 months, 80% of patients had a complete or partial response after one treatment, and the remaining 20% required a secondary procedure.

Joeris et al15 reported on 23 patients treated with percunateous tricalcium sulphate, with a rate of healing of 96%. Another study reported on 13 patients treated with calcium phosphate pellets, with all defects healing in a mean of 13.4 weeks.16

Hou et al17 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 cauterisation, ablation of cyst with an impactor, calcium sulphate pellets, and placement of a screw.17

Donaldson and Wright18 commented that the lack of clear patho-aetiology 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 randomised controlled trial.19

Revision hip arthroplasty

A major challenge in revision hip surgery is addressing loss of bone stock on either the femoral or 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 randomised 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 and Blom21 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 six 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 undergoing 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 morcellised 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 ten 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.


This article was originally published in the Canadian Orthopaedic Association’s COA Bulletin #95, Winter 2011 edition



1. Finkemeier CG. Bone-grafting and bone-graft substitutes. J Bone Joint Surg [Am] 2002;84-A:454-64.

2. Van Heest A, Swiontkowski M. Bone-graft substitutes. Lancet 1999;353(Suppl):SI28-29.

3. Van der Stok J, Van Lieshout EM, El-Massoudi Y, Van Kralingen GH, Patka P. Bone substitutes in the Netherlands: a systematic literature review. Acta Biomater 2011;7:739-50.

4. Nandi SK, Roy S, Mukherjee P, et al. Orthopaedic applications of bone graft and graft substitutes: a review. Ind J Med Res 2010;132:15-30.

5. 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. Eur Spine J 2008;17:845-52.

6. Summers BN, Eisenstein SM. Donor site pain from the ilium: a complication of lumbar spine fusion. J Bone Joint Surg [Br] 1989;71-B:677-80.

7. Seiler JG 3rd, Johnson J. Iliac crest autogenous bone grafting: donor site complications. J South Orthop Assoc 2000;9:91-7.

8. Boyce T, Edwards J, Scarborough N. Allograft bone: the influence of processing on safety and performance. Orthop Clin North Am 1999;30:571-81.

9. Siegel HJ, Baird RC 3rd, Hall J, Lopez-Ben R, Lander PH. The outcome of composite bone graft substitute used to treat cavitary bone defects. Orthopedics 2008;31:754-4.

10. El-Adl G, Mostafa MF, Enan A, Ashraf M. Biphasic ceramic bone substitute mixed with autogenous bone marrow in the treatment of cavitary benign bone lesions. Acta Orthop Belg 2009;75:110-18.

11. Shibuya K, Kurosawa H, Takeuchi H, Niwa S. The medium-term results of treatment with hydroxyapatite implants. J Biomed Mater Res B Appl Biomater 2005;75:405-13.

12. Faour O, Dimitriou R, Cousins CA, Giannoudis PV. The use of bone graft substitutes in large cancellous voids: any specific needs? Injury 2011;42(Suppl2):S87-90.

13. Thawrani D, Thai CC, Welch RD, Copley L, Johnston CE. Successful treatment of unicameral bone cyst by single percutaneous injection of alpha-BSM. J Pediatr Orthop 2009;29:511-17.

14. Mik G, Arkader A, Manteghi A, Dormans JP. Results of a minimally invasive technique for treatment of unicameral bone cysts. Clin Orthop Relat Res 2009;467:2949-54.

15. Joeris A, Ondrus S, Planka L, Gal P, Slongo T. ChronOS inject in children with benign bone lesions: does it increase the healing rate? Eur J Pediatr Surg 2010;20:24-8.

16. Mirzayan R, Panossian V, Avedian R, Forrester DM, Menendez LR. The use of calcium sulfate in the treatment of benign bone lesions: a preliminary report. J Bone Joint Surg [Am] 2001;83-A:355-8.

17. Hou HY, Wu K, Wang CT, et al. Treatment of unicameral bone cyst: a comparative study of selected techniques. J Bone Joint Surg [Am] 2010;92-A:855-62.

18. Donaldson S, Wright JG. Recent developments in treatment for simple bone cysts. Curr Opin Pediatr 2011;23:73-7.

19. Wright JG, Yandow S, Donaldson S, Marley L. A randomized clinical trial comparing intralesional bone marrow and steroid injections for simple bone cysts. J Bone Joint Surg [Am] 2008;90-A:722-30.

20. Slooff TJ, Buma P, Schreurs BW, et al. Acetabular and femoral reconstruction with impacted graft and cement. Clin Orthop Relat Res 1996;324:108-15.

21. Beswick A, Blom AW. Bone graft substitutes in hip revision surgery: a comprehensive overview. Injury 2011;42(Suppl 2):S40-6.

22. Aulakh TS, Jayasekera N, Kuiper JH, Richardson JB. Long-term clinical outcomes following the use of synthetic hydroxyapatite and bone graft in impaction in revision hip arthroplasty. Biomaterials 2009;30:1732-8.

23. Blom AW, 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 Orthop 2009;80:150-4.

24. Engelbrecht E, von Foerster G, Delling G. Ionogran in revision arthroplasty. J Bone Joint Surg [Br] 2000;82-B:192-9.

25. 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 2008;31:277-7.

26. Kawanabe K, Iida H, Matsusue Y, et al. A-W glass ceramic as a bone substitute in cemented hip arthroplasty: 15 hips followed 2-10 years. Acta Orthop Scand 1998;69:237-42.

27. McNamara IR. Impaction bone grafting in revision hip surgery: past, present and future. Cell Tissue Banking 2010;11:57-73.

28. Muller M, Stangl R. Norian SRS augmentation in revision of acetabular cup of total hip arthroplasty: a follow up of six patients. Der Unfallchirurg 2006;109:335-8 (in German).

29. Egawa H, Ho H, Huynh C, et al. A three-dimensional method for evaluating changes in acetabular osteolytic lesions in response to treatment. Clin Orthop Relat Res 2010;468:480-90.

30. Nich C, Sedel L. Bone substitution in revision hip replacement. Int Orthop 2006;30:525-31.

31. Nishii T, Sugano N, Miki H, Koyama T, Yoshikawa H. Multidetector-CT evaluation of bone substitutes remodeling after revision hip surgery. Clin Orthop Relat Res 2006;442:158-64.

32. 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. J Bone Joint Surg [Br] 1997;79-B:87-92.

33. Wasielewski RC, Sheridan KC, Lubbers MA. Coralline hydroxyapatite in complex acetabular reconstruction. Orthopedics 2008;31:367-7.

34. 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. J Mater Sci Mater Med 1999;10:821-5.

35. 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). J Bone Joint Surg [Br] 2010;92-B:617-23.