In Vitro Elution Characteristics of Vancomycin in a Composite Calcium Phosphate/Calcium Sulfate Bone Substitute



Periprosthetic joint infection is a particularly difficult orthopedic problem, complicating a growing number of revision procedures. Joint debridement and systemic antibiotics are the mainstay of treatment, yet difficulty remains in maintaining a minimum inhibitory concentration of antibiotic at the localized site of infection.

Study Aims

This study analyzes the elution characteristics of a 40%bwt calcium phosphate–60%bwt calcium sulfate composite, at varying concentrations of vancomycin.


Four groups of varying concentrations of vancomycin (2.63%bwt, 5.13%, 9.76%, and 17.78%) were mixed with one pack of the composite cement. At designated time intervals up to 28 days, the antibiotic concentration was detected using fluorescence polarization immunoassay and the elution trends compared.


The elution rate of each of the four groups decreased over time. At almost all of the intervals, the elution rates of the higher concentration groups were significantly higher than the lower concentration groups (P < 0.05).


Calcium sulfate reabsorbs over a prolonged period, producing porosity which allows for new bone ingrowth through occupation of osteoprogenitor cells and osteoblasts; while calcium phosphate acts as a long-term osteoconductive matrix.

Clinical Relevance

The results of this study suggest that vancomycin can be mixed affectively with a calcium sulfate/phosphate composite, both maintaining stability and eluting gradually over a clinically relevant period of time.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. 1.

    Adams K, Couch L, Cierny G, Calhoun J, Mader JT. (1992) In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop 8:244–52

    Google Scholar 

  2. 2.

    Beuerlein M, McKee M. (2010) Calcium sulfates: what is the evidence? J Orthop Trauma 24:46–51

    Article  Google Scholar 

  3. 3.

    Böstman OM, Laitinen OM, Tynninen O, Salminen ST, Pihlajamäki HK. (2005) Tissue restoration after resorption of polyglycolide and poly-laevo-lactic acid screws. J Bone Joint Surg (Br). 87: 1575–80

    Article  Google Scholar 

  4. 4.

    Buchholz H, Elson R, Heinert K. (1984) Antibiotic loaded acrylic cement. Clin Orthop Relat Res. 190:96–108

    PubMed  Google Scholar 

  5. 5.

    Calhoun JH, Manring MM, Shirtliff M (2009) Osteomyelitis of the long bones.. Semin Plast Surg. 23:59–72.

    PubMed  Article  Google Scholar 

  6. 6.

    Hernandez-Soria A, Yang X, Reinhart J, Ricciardi BF, Bostrom M. In vitro elution characteristics of antibiotic laden hydroxyapatite bone cement. Abstract 0924, 52nd Annual Meeting of the Orthopaedic Research Society

  7. 7.

    Holmes RE, Mooney V. (1984) A coralline hydroxyapatite bone graft substitute. Clin. Orthop.188: 252–62

    PubMed  CAS  Google Scholar 

  8. 8.

    Jaeblon T. (2010) Polymethylmethacrylate: properties and contemporary uses in orthopaedics. J Am Acad Orthop Surg. 18:297–305. Review

    PubMed  Google Scholar 

  9. 9.

    Kelly CM, Wilkins RW, Gitelis S, Hartjen C, Watson JT, Kim PT. (2001) The use of a surgical grade calcium sulfate as a bone graft substitute: results of a multicenter trial. Clin Orthop Relat Res. 382:42–50

    PubMed  Article  Google Scholar 

  10. 10.

    Lazzarini L, Mader JT, Calhoun JH (2004) Osteomyelitis in long bones. J Bone Joint Surg Am. 86:2305–2318

    PubMed  Google Scholar 

  11. 11.

    McKee MD, Wild LM, Schemitsch EH, Waddell JP. (2002) The use of an antibiotic-impregnated, osteoconductive, bioabsorbable bone substitute in the treatment of infected long bone defects: early results of a prospective trial. J Orthop Trauma 16:622–7.

    PubMed  Article  Google Scholar 

  12. 12.

    Moojen DJ, Hentenaar B, Charles Vogely H, Verbout AJ, Castelein RM, Dhert WJ.(2008) In vitro release of antibiotics from commercial PMMA beads and articulating hip spacers. J Arthroplasty. 23:1152–6.

    PubMed  Article  Google Scholar 

  13. 13.

    Moore W, Graves S, Bain G. (2001) Synthetic bone graft substitutes. ANZ J Surg. 71:354–61

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Mousset B, Benoit MA, Delloye C, Bouillet R, Gillard J. (1995) Biodegradable implants for potential use in bone infection. An in vitro study of antibiotic-loaded calcium sulphate. Int Orthop. 19: 157–161

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Neut D, Kluin OS, Crielaard BJ, van der Mei HC, Busscher HJ, Grijpma DW (2009) A biodegradable antibiotic delivery system based on poly-(trimethylene carbonate) for the treatment of osteomyelitis. Acta Orthop. 80:514–9.

    PubMed  Article  Google Scholar 

  16. 16.

    Neut D, van de Belt H, van Horn JR, van der Mei HC, Busscher HJ. (2003) Residual gentamicin-release from antibiotic-loaded polymethylmethacrylate beads after 5 years of implantation. Biomaterials. 24: 1829–31.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Peltier LF, Jones RH. (2004) Treatment of unicameral bone cysts by curettage and packing with plaster-of-paris pellets. Clin Orthop Relat Res. 422:145–147

    PubMed  Article  Google Scholar 

  18. 18.

    Rahimi F, Maurer BT, Enzweiler MG. (1997) Coralline Hydroxyapatite: A Bone Graft Alternative in Foot and Ankle Surgery. The Journal of Foot & Ankle Surgery. 36:192–203

    Article  CAS  Google Scholar 

  19. 19.

    Rajzer I, Castaño O, Engel E, Planell JA. (2010) Injectable and fast resorbable calcium phosphate cement for body-setting bone grafts. J Mater Sci Mater Med. Accessed 12th May 2010

  20. 20.

    Shirtliff ME, Calthoun JH, Mader JT. (2002) Experimental osteomyelitis treatment with antibiotic impregnated hydroxyapatite. Clin Orthop. 401, 239–47

    PubMed  Article  Google Scholar 

  21. 21.

    Solberg BD, Gutow AP, Baumgaertner MR. (1999) Efficacy of gentamycin-impregnated resorbable hydroxyapatite cement in treating osteomyelitis in a rat model. J Orthop Trauma. 13:102–6.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Stevens CM, Tetsworth KD, Calhoun JH, Mader JT. (2005) An articulated antibiotic spacer used for infected total knee arthroplasty: a comparative in vitro elution study of Simplex® and Palacos® bone cements J Orthop Res. 23: 27–33

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Strocchi R,Orsini G,Iezzi G,Scarano A,Rubini C,Pecora G,Piattelli A. (2002) Bone regeneration with calcium sulfate: Evidence for increased angiogenesis in rabbits. J Oral Implantol 28:273–278

    PubMed  Article  Google Scholar 

  24. 24.

    Turner TM, Urban RM, Gitelis S, Kuo KN, Andersson GBJ. (2001) Radiographic and histologic assessment of calcium sulfate in experimental animal models and clinical use as a resorbable bone-graft substitute, a bone-graft expander, and a method for local antibiotic delivery: one institution’s experience. J Bone Joint Surg Am. 83(suppl 2):8–18.

    PubMed  Google Scholar 

  25. 25.

    Urban RM, Turner TM, Hall DJ, Infanger S, Cheema N, Lim TH. (2003) Healing in large defects with calcium sulfate pellets containing demineralized bone particles. Orthopedics. 26(5 suppl): S581–S585.

    PubMed  Google Scholar 

  26. 26.

    Urban RM, Turner TM, Hall DJ, Infanger SI, Cheema N, Lim TH, Moseley J, Carroll M, Roark M. (2004) Effects of altered crystalline structure and increased initial compressive strength of calcium sulfate bone graft substitutes on new bone formation. Orthopedics. 27(1 suppl):S113–S118.

    PubMed  Google Scholar 

  27. 27.

    Walenkamp G. (1997) How i do it: chronic osteomyelitis. Acta Orthop Scand. 68:497–506

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Walsh WR, Morberg P, Yu Y, Yang JL, Haggard W, Sheath PC, Svehla M, Bruce JM. (2003) Response of calcium sulfate bone graft substitute in a confined cancellous defect. Clin Orthop Relat Res. 406:228–236

    PubMed  Article  Google Scholar 

Download references


Bone Support AB, the manufacturer of Cerament, supplied the material for the study.


One or more of the authors (MB) has received funding from Bone Support.

Author information



Corresponding author

Correspondence to Liza Osagie MBBS.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yang, X., Osagie, L. & Bostrom, M.P. In Vitro Elution Characteristics of Vancomycin in a Composite Calcium Phosphate/Calcium Sulfate Bone Substitute. HSS Jrnl 8, 129–132 (2012).

Download citation


  • antibiotic delivery
  • drug delivery
  • bone infection