Skip to main content
SpringerLink
Log in

Osteopenic bone cell response to strontium-substituted hydroxyapatite

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Ionic substitution is a powerful tool to improve the biological performance of calcium phosphate based materials. In this work, we investigated the response of primary cultures of rat osteoblasts derived from osteopenic (O-OB) bone to strontium substituted hydroxyapatite (SrHA), and to hydroxyapatite (HA) as reference material, compared to normal (N-OB) bone cells. Strontium (Sr) and calcium (Ca) cumulative releases in physiological solution are in agreement with the greater solubility of SrHA than HA, whereas the differences between the two materials are levelled off in DMEM, which significantly reduced ion release. O-OB cells grown on SrHA exhibited higher proliferation and increased values of the differentiation parameters. In particular, Sr substitution increased the levels of proliferation, alkaline phosphatase, and collagen type I, and down-regulated the production of interleukin-6 of O-OB cells, demonstrating a promising future of SrHA in the treatment of bone lesions and defects in the presence of osteoporotic bone.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Dimitrious R, Babis GC. Biomaterial osseointegration enhancement with biophysical stimulation. J Musculoskelet Neuronal Interact. 2007;7:253–65.

    Google Scholar 

  2. Lind M, Bunger C. Factors stimulating bone formation. Eur Spine J. 2001;10:S102–9.

    Article  Google Scholar 

  3. Calvo-Fernandez T, Parra J, Fernandez-Gutierrez M, Vasquez-Lasa B, Lopez-Bravo A, Collia F, Perez de la Cruz MA, San Roman J. Biocompatbility of alendronate-loaded acrylic cement for vertebroplasty. Eur Cells Mater. 2010;20:260–73.

    CAS  Google Scholar 

  4. Marie PJ. Strontium ranelate: a novel mode of action optimizing bone formation and resorption. Osteoporos Int. 2005;16:S7–10.

    Article  CAS  Google Scholar 

  5. Ammann P. Strontium ranelate: a novel mode of action leading to renewed bone quality. Osteoporos Int. 2005;16:S11–5.

    Article  CAS  Google Scholar 

  6. Deeks ED, Dhillon S. Strontium ranelate: a review of its use in the treatment of postmenopausal osteoporosis. Drugs. 2010;70:733–59.

    Article  CAS  Google Scholar 

  7. Gallacher SJ, Dixon T. Impact of treatments for postmenopausal osteoporosis (biphosphonates, parathyroid hormone, strontium ranelate and denosumab) on bone quality: a systematic review. Calcif Tissue Int. 2010;87:469–84.

    Article  CAS  Google Scholar 

  8. Dahl SG, Allain P, Marie PJ, Mauras Y, Boivin G, Ammann P, Tsouderos Y, Delmas PD, Christiansen C. Incorporation and distribution of strontium in bone. Bone. 2001;28:446–53.

    Article  CAS  Google Scholar 

  9. Marie PJ, Ammann P, Boivin G, Rey C. Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int. 2001;69:121–9.

    Article  CAS  Google Scholar 

  10. Bonnelye E, Chabadel A, Saltel F, Jurdic P. Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone. 2008;42:129–38.

    Article  CAS  Google Scholar 

  11. Marie PJ, Hott M, Modrowski D, Depollak C, Guillemain J, Deloffre P, Tsouderos P. An uncoupling agent containing strontium prevents bone loss by depressing bone-resorption and maintaining bone-formation in estrogen-deficient rats. J Bone Miner Res. 1993;8:607–15.

    Article  CAS  Google Scholar 

  12. Reginster JY, Bruyère O, Sawicki A, Roces-Varela A, Fardellone P, Roberts A, Devogelaer JP. Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years. Bone. 2009;45:1059–64.

    Article  CAS  Google Scholar 

  13. Xue W, Hosick HL, Bandyopadhyay A, Bose S, Ding C, Luk KDK, Cheung KMC, Lu WW. Preparation and cell-materials interactions of plasma sprayed strontium-containing hydroxyapatite coating. Surf Coat Technol. 2007;201:4685–93.

    Article  CAS  Google Scholar 

  14. Capuccini C, Torricelli P, Sima F, Boanini E, Ristoscu C, Bracci B, Socol G, Fini M, Mihailescu IN, Bigi A. Strontium-substituted hydroxyapatite coatings synthesized by pulsed-laser deposition: in vitro osteoblast and osteoclast response. Acta Biomater. 2008;4:1885–93.

    Article  CAS  Google Scholar 

  15. Gentleman E, Fredholm YC, Jell G, Lotfibakhshaiesh N, O’Donnell MD, Hill RG, Stevens MM. The effects of strontium-substituted bioactive glasses on osteoblasts and osteoclasts in vitro. Biomaterials. 2010;31:3949–56.

    Article  CAS  Google Scholar 

  16. Isaac J, Nohra J, Lao J, Jallot E, Nedelec JM, Berdal A, Sautier JM. Effects of strontium-doped bioactive glass on the differentiation of cultured osteogenic cells. Eur Cells Mater. 2011;21:130–43.

    CAS  Google Scholar 

  17. Boanini E, Gazzano M, Bigi A. Ionic substitutions in calcium phosphates synthesized at low temperature. Acta Biomater. 2010;6:1882–94.

    Article  CAS  Google Scholar 

  18. Capuccini C, Torricelli P, Boanini E, Gazzano M, Giardino R, Bigi A. Interaction of Sr-doped hydroxyapatite nanocrystals with osteoclast and osteoblast-like cells. J Biomed Mater Res. 2009;89A:594–600.

    Article  CAS  Google Scholar 

  19. Zhang H, Lewis CG, Aronow MS, Gronowicz GA. The effects of patient age on human osteoblast’ response to Ti-6Al-4 V implants in vitro. J Orthop Res. 2004;22:30–8.

    Article  CAS  Google Scholar 

  20. Fini M, Giavaresi G, Torricelli P, Krajewski A, Ravaglioli A, Belmonte MM, Biagini G, Giardino R. Biocompatibility and osseintegration in osteoporotic bone. A preliminary in vitro and in vivo study. J Bone and Joint Surg (Br). 2001;1(83B):139–43.

    Article  Google Scholar 

  21. Torricelli P, Fini M, Rocca M, Giavaresi G, Giardino R. In vitro pathological model of osteopenia to test orthopaedic biomaterials. Art Cells Blood Subst Immobil Biotechnol. 2000;28:181–92.

    Article  CAS  Google Scholar 

  22. Fini M, Giavaresi G, Nicoli Aldini N, Torricelli P, Morrone G, Guzzardella GA, Giardino R, Krajewski A, Ravaglioli A, Mattioli Belmonte M, De Benedittis A, Biagini G. The effect of osteopenia on the osteointegration of different biomaterials: histomorphometric study in rats. J Mater Sci: Mater Med. 2000;11:579–85.

    Article  CAS  Google Scholar 

  23. Bigi A, Boanini E, Capuccini C, Gazzano M. Strontium-substituted hydroxyapatite nanocrystals. Inorg Chim Acta. 2007;360:1009–16.

    Article  CAS  Google Scholar 

  24. Giavaresi G, Fini M, Gnudi S, De Terlizzi F, Carpi A, Giardino R. The femoral distal epiphysis of ovariectomized rats as a site for studies on osteoporosis: structural and mechanical evaluations. Clin Exp Rheumatol. 2002;20:171–8.

    CAS  Google Scholar 

  25. Klug HP, Alexander LE. X-ray diffraction procedures for polycrystalline and amorphous materials. New York: Wiley-Interscience; 1974.

    Google Scholar 

  26. Terra J, Rodrigues Dourado E, Eon JG, Ellis DE, Gonzalez G, Malta Rossi A. The structure of strontium-doped hydroxyapatite: an experimental and theoretical study. Phys Chem Chem Phys. 2009;11:568–77.

    Article  CAS  Google Scholar 

  27. O’Donnell MD, Fredholm Y, de Rouffignac A, Hill RG. Structural analysis of a series of strontium-substituted apatites. Acta Biomater. 2008;4:1455–64.

    Article  Google Scholar 

  28. Pan HB, Li ZY, Lam WM, Wong JC, Darvell BW, Luk KDK, Lu WW. Solubility of strontium-substituted apatite by solid titration. Acta Biomater. 2009;5:1678–85.

    Article  CAS  Google Scholar 

  29. Landi E, Sprio S, Sandri M, Celotti G, Tampieri A. Development of Sr and CO3 co-substituted hydroxyapatites for biomedical applications. Acta Biomater. 2008;4:656–63.

    Article  CAS  Google Scholar 

  30. Torricelli P, Fini M, Giavaresi G, Giardino R. Osteoblasts cultured from osteoporotic bone: a comparative investigation on human and animal-derived cells. Art Cells Blood Subs Immob Biotech. 2003;31(3):263–77.

    Article  CAS  Google Scholar 

  31. Bigi A, Panzavolta S, Sturba L, Torricelli P, Fini M, Giardino R. Normal and osteopenic bone derived osteoblast response to a biomimetic gelatin–calcium phosphate bone cement. J Biomed Mater Res. 2006;78A:739–45.

    Article  CAS  Google Scholar 

  32. Marie PJ. Cellular and molecular alterations of osteoblasts in human disorders of bone formation. Histol Histopathol. 1999;14:525–38.

    CAS  Google Scholar 

  33. Scheidt-Nave C, Bismar H, Leidig-Bruckner G, Woitge H, Seibel MJ, Ziegler R, Pfeilschifter J. Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause. J Clin Endocrinol Metab. 2001;86:2032–42.

    Article  CAS  Google Scholar 

  34. Pino AM, Rıos S, Astudillo P, Fernandez M, Figueroa P, Seitz G, Rodrıguez JP. Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women. J Bone Miner Res. 2010;25:492–8.

    Article  CAS  Google Scholar 

  35. Malaval L, Liu F, Roche P, Aubin JE. Kinetics of osteoprogenitor proliferation and osteoblast differentiation in vitro. J Cell Biochem. 1999;74:616–27.

    Article  CAS  Google Scholar 

  36. Atsushi E, Korenori O, Satoshi I, Shigeyuki E, Takayoshi N, Yukichi U. Effects of α-TCP and TetCP on MC3T3–E1 proliferation, differentiation and mineralization. Biomaterials. 2003;24:831–6.

    Article  Google Scholar 

  37. Franceschi RT, Iyer BS. Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3–E1 cells. J Bone Miner Res. 1992;7:235–46.

    Article  CAS  Google Scholar 

  38. Cowles EA, DeRome D, Pastizzo G, Brailey LL, Gronowicz GA. Mineralization and the expression of matrix proteins during in vivo bone development. Calcif Tissue Int. 1998;62:74–82.

    Article  CAS  Google Scholar 

  39. Fini M, Giardino R, Borsari V, Torricelli P, Rimondini L, Giavaresi G, Nicoli Aldini N. In vitro behaviour of osteoblasts cultured on orthopaedic biomaterials with different surface roughness, uncoated and fluorohydroxyapatite-coated, relative to the in vivo osteointegration rate. Int J Artif Organs. 2003;26:520–8.

    CAS  Google Scholar 

  40. Mayr-Wohlfart U, Fiedler J, Gunther KP, Puhl W, Kessler S. Proliferation and differentiation rates of a human osteoblast-like cell line (SaOS-2) in contact with different bone substitute materials. J Biomed Mater Res. 2001;57:132–9.

    Article  CAS  Google Scholar 

  41. Kishimoto T, Akira S, Taga T. Interleukin-6 and its receptor: a paradigm for cytokines. Science. 1992;258(5082):593–7.

    Article  CAS  Google Scholar 

  42. Axmann R, Böhm C, Krönke G, Zwerina J, Smolen J, Schett G. Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum. 2009;60(9):2747–56.

    Article  CAS  Google Scholar 

  43. Blanchard F, Duplomb L, Baud’hium M, Brounais B. The dual role of IL-6type cytokines on bone remodeling and bone tumors. Cytokine Growth Factor Rev. 2009;20:19–28.

    Article  CAS  Google Scholar 

  44. MacEwan DJ. TNF ligands and receptors: a matter of life and death. Br J Pharmacol. 2002;135:855–75.

    Article  CAS  Google Scholar 

  45. Steeve KT, Marc P, Sandrine T, Dominique H, Yannick F. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15:49–60.

    Article  CAS  Google Scholar 

  46. Atkins GJ, Welldon KJ, Halbout P, Findlay DM. Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int. 2009;20:653–64.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was carried out with the financial support of MIUR.

Author information

Authors and Affiliations

  1. Department of Chemistry “G. Ciamician”, University of Bologna, 40126, Bologna, Italy

    E. Boanini & A. Bigi

  2. Laboratory of Preclinical and Surgical Studies, Research Institute Codivilla Putti, Rizzoli Orthopaedic Institute, Bologna, Italy

    P. Torricelli & M. Fini

Authors
  1. E. Boanini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Torricelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Fini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Bigi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Bigi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boanini, E., Torricelli, P., Fini, M. et al. Osteopenic bone cell response to strontium-substituted hydroxyapatite. J Mater Sci: Mater Med 22, 2079–2088 (2011). https://doi.org/10.1007/s10856-011-4379-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-011-4379-3

Keywords

Search

Navigation