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Effects of strontium on the quality of bone apatite crystals: a paired biopsy study in postmenopausal osteoporotic women

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Abstract

Summary

In paired biopsies of osteoporotic women treated with either strontium ranelate or a placebo for 36 months, characteristics of bone apatite crystals were not influenced by the presence of strontium. The mean rate of substitutions of calcium by strontium ions was 4.5 %.

Introduction

The potential effect of strontium (Sr) on bone apatite crystals was investigated in paired biopsies of osteoporotic women treated with either strontium ranelate (SrRan) or a placebo for 36 months.

Methods

In ten paired biopsies, crystallinity, apparent length and width/thickness of crystals, interplanar distances, and lattice parameters of unit cells were assessed by X-ray diffraction and selected area electron diffraction.

Results

All these parameters, reflecting crystal and unit cell characteristics, were not influenced by the presence of Sr and were similar in SrRan and placebo groups after 36 months of treatment. The mean rate of substitutions of calcium by Sr ions was 4.5 %.

Conclusion

Overall, the quality of bone apatite crystals was maintained after 36 months of treatment with SrRan.

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References

  1. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468

    Article  PubMed  CAS  Google Scholar 

  2. Meunier PJ, Roux C, Ortolani S, Diaz-Curiel M, Compston J, Marquis P, Cormier C, Isaia G, Badurski J, Wark JD, Collette J, Reginster JY (2009) Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis. Osteoporos Int 20:1663–1673

    Article  PubMed  CAS  Google Scholar 

  3. Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, Curiel MD, Sawicki A, Goemaere S, Sorensen OH, Felsenberg D, Meunier PJ (2005) Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab 90:2816–2822

    Article  PubMed  CAS  Google Scholar 

  4. Reginster JY, Bruyere O, Sawicki A, Roces-Varela A, Fardellone P, Roberts A, Devogelaer JP (2009) Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years. Bone 45:1059–1064

    Article  PubMed  CAS  Google Scholar 

  5. Rolland Y, Abellan Van Kan G, Gillette-Guyonnet S, Roux C, Boonen S, Vellas B (2011) Strontium ranelate and risk of vertebral fractures in frail osteoporotic women. Bone 48:332–338

    Article  PubMed  CAS  Google Scholar 

  6. Seeman E, Devogelaer JP, Lorenc R, Spector T, Brixen K, Balogh A, Stucki G, Reginster JY (2008) Strontium ranelate reduces the risk of vertebral fractures in patients with osteopenia. J Bone Miner Res 23:433–438

    Article  PubMed  CAS  Google Scholar 

  7. Seeman E, Boonen S, Borgstrom F, Vellas B, Aquino JP, Semler J, Benhamou CL, Kaufman JM, Reginster JY (2010) Five years treatment with strontium ranelate reduces vertebral and nonvertebral fractures and increases the number and quality of remaining life-years in women over 80 years of age. Bone 46:1038–1042

    Article  PubMed  CAS  Google Scholar 

  8. Turner CH (2002) Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int 13:97–104

    Article  PubMed  CAS  Google Scholar 

  9. Follet H, Boivin G, Rumelhart C, Meunier PJ (2004) The degree of mineralization is a determinant of bone strength: a study on human calcanei. Bone 34:783–789

    Article  PubMed  CAS  Google Scholar 

  10. Fratzl P, Gupta H, Paschalis E, Roschger P (2004) Structure and mechanical quality of the collagen–mineral nano-composite in bone. J Mater Chem 14:2115–2123

    Article  CAS  Google Scholar 

  11. Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261

    Article  PubMed  CAS  Google Scholar 

  12. Bouxsein ML (2005) Determinants of skeletal fragility. Best Pract Res Clin Rheumatol 19:897–911

    Article  PubMed  Google Scholar 

  13. Boivin G, Farlay D, Khebbab MT, Jaurand X, Delmas PD, Meunier PJ (2010) In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization. Osteoporos Int 21:667–677

    Article  PubMed  CAS  Google Scholar 

  14. Roschger P, Manjubala I, Zoeger N, Meirer F, Simon R, Li C, Fratzl-Zelman N, Misof BM, Paschalis EP, Streli C, Fratzl P, Klaushofer K (2010) Bone material quality in transiliac bone biopsies of postmenopausal osteoporotic women after 3 years of strontium ranelate treatment. J Bone Miner Res 25:891–900

    Article  PubMed  Google Scholar 

  15. Doublier A, Farlay D, Khebbab MT, Jaurand X, Meunier PJ, Boivin G (2011) Distribution of strontium and mineralization in iliac bone biopsies from osteoporotic women treated long-term with strontium ranelate. Eur J Endocrinol 165:469–476

    Article  PubMed  CAS  Google Scholar 

  16. Heijligers HJ, Driessens FC, Verbeeck RM (1979) Lattice parameters and cation distribution of solid solutions of calcium and strontium hydroxyapatite. Calcif Tissue Int 29:127–131

    Article  PubMed  CAS  Google Scholar 

  17. Christoffersen J, Christoffersen MR, Kolthoff N, Barenholdt O (1997) Effects of strontium ions on growth and dissolution of hydroxyapatite and on bone mineral detection. Bone 20:47–54

    Article  PubMed  CAS  Google Scholar 

  18. Verberckmoes SC, Behets GJ, Oste L, Bervoets AR, Lamberts LV, Drakopoulos M, Somogyi A, Cool P, Dorrine W, De Broe ME, D’Haese PC (2004) Effects of strontium on the physicochemical characteristics of hydroxyapatite. Calcif Tissue Int 75:405–415

    Article  PubMed  CAS  Google Scholar 

  19. Bigi A, Boanini E, Capuccini C, Gazzano M (2007) Strontium-substituted hydroxyapatite nanocrystals. Inorg Chim Acta 360:1009–1016

    Article  CAS  Google Scholar 

  20. O’Donnell MD, Fredholm Y, de Rouffignac A, Hill RG (2008) Structural analysis of a series of strontium-substituted apatites. Acta Biomater 4:1455–1464

    Article  PubMed  Google Scholar 

  21. Li ZY, Lam WM, Yang C, Xu B, Ni GX, Abbah SA, Cheung KM, Luk KD, Lu WW (2007) Chemical composition, crystal size and lattice structural changes after incorporation of strontium into biomimetic apatite. Biomaterials 28:1452–1460

    Article  PubMed  CAS  Google Scholar 

  22. Boanini E, Torricelli P, Fini M, Bigi A (2011) Osteopenic bone cell response to strontium-substituted hydroxyapatite. J Mater Sci Mater Med 22:2079–2088

    Article  PubMed  CAS  Google Scholar 

  23. Boivin G, Deloffre P, Perrat B, Panczer G, Boudeulle M, Mauras Y, Allain P, Tsouderos Y, Meunier PJ (1996) Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J Bone Miner Res 11:1302–1311

    Article  PubMed  CAS  Google Scholar 

  24. Cazalbou S, Combes C, Rey C (2002) S12911 treatment maintains bone mineral characteristics. J Bone Miner Res 17:S376

    Google Scholar 

  25. LeGeros R, Lin S, LeGeros J (2003) Strontium ranelate treatment preserves bone crystal characteristics and dissolution properties of bone apatite. J Bone Miner Res 18:S276

    Google Scholar 

  26. Farlay D, Boivin G, Panczer G, Lalande A, Meunier PJ (2005) Long-term strontium ranelate administration in monkeys preserves characteristics of bone mineral crystals and degree of mineralization of bone. J Bone Miner Res 20:1569–1578

    Article  PubMed  CAS  Google Scholar 

  27. Bunger MH, Oxlund H, Hansen TK, Sorensen S, Bibby BM, Thomsen JS, Langdahl BL, Besenbacher F, Pedersen JS, Birkedal H (2010) Strontium and bone nanostructure in normal and ovariectomized rats investigated by scanning small-angle X-ray scattering. Calcif Tissue Int 86:294–306

    Article  PubMed  Google Scholar 

  28. Li Z, Lu WW, Deng L, Chiu PK, Fang D, Lam RW, Leong JC, Luk KD (2010) The morphology and lattice structure of bone crystal after strontium treatment in goats. J Bone Miner Metab 28:25–34

    Article  PubMed  Google Scholar 

  29. Li C, Paris O, Siegel S, Roschger P, Paschalis EP, Klaushofer K, Fratzl P (2010) Strontium is incorporated into mineral crystals only in newly formed bone during strontium ranelate treatment. J Bone Miner Res 25:968–975

    PubMed  CAS  Google Scholar 

  30. Labar JL (2005) Consistent indexing of a (set of) single crystal SAED pattern(s) with the ProcessDiffraction program. Ultramicroscopy 103:237–249

    Article  PubMed  CAS  Google Scholar 

  31. Rey C, Combes C, Drouet C, Glimcher MJ (2009) Bone mineral: update on chemical composition and structure. Osteoporos Int 20:1013–1021

    Article  PubMed  CAS  Google Scholar 

  32. Robinson RA (1952) An electron-microscopic study of the crystalline inorganic component of bone and its relationship to the organic matrix. J Bone Joint Surg Am 34-A:389–435, passim

    PubMed  CAS  Google Scholar 

  33. Weiner S, Traub W (1992) Bone structure: from angstroms to microns. FASEB J 6:879–885

    PubMed  CAS  Google Scholar 

  34. Parfitt AM (2002) Misconceptions (2): turnover is always higher in cancellous than in cortical bone. Bone 30:807–809

    Article  PubMed  CAS  Google Scholar 

  35. Cazalbou S, Combes C, Rey C (2001) Biomimetic approach for strontium-containing Ca-P bioceramics with enhanced biological activity. Key Eng Mater 192–195:147–150

    Article  Google Scholar 

  36. Nakano T, Kaibara K, Tabata Y, Nagata N, Enomoto S, Marukawa E, Umakoshi Y (2002) Unique alignment and texture of biological apatite crystallites in typical calcified tissues analyzed by microbeam X-ray diffractometer system. Bone 31:479–487

    Article  PubMed  CAS  Google Scholar 

  37. Yalin S, Comelekoglu U, Bagis S, Yilmaz N (2012) Effects of strontium ranelate on cortical bone collagen integrity. Saudi Med J 33:515–519

    PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Servier (Suresnes, France) and by Institut National de la Santé et de la Recherche Médicale. The expert assistance of Gérard Panczer (Laboratoire de Physico-Chimie des Matériaux Luminescents–UMR 5620, Université de Lyon, Villeurbanne, France), Erwann Jeanneau (Centre de diffractométrie Henri Longchambon, Université de Lyon, Villeurbanne, France), and Pr Christian Rey (ENSIACET, Toulouse, France) was also gratefully appreciated. The authors thank the three anonymous reviewers for their constructive and extensive critiques that guided a considerable improvement of our manuscript.

Manufacturer name

Strontium ranelate is manufactured by Servier as Protelos®, Protos®, Protaxos®, Osseor®, and Bivalos®.

Disclaimers

The authors have received an unrestricted grant from Servier.

Conflicts of interest

Georges Boivin serves as a consultant for Servier. All other authors have no conflicts of interest.

Author information

Authors and Affiliations

  1. INSERM, UMR 1033, 69372, Lyon, France

    A. Doublier, D. Farlay & G. Boivin

  2. Université de Lyon, 69008, Lyon, France

    A. Doublier, D. Farlay & G. Boivin

  3. Centre Technologique des Microstructures, Université de Lyon, 69622, Villeurbanne, France

    X. Jaurand

  4. Centre de diffractométrie Henri Longchambon, Université de Lyon, 69622, Villeurbanne, France

    R. Vera

  5. Faculté de Médecine Lyon-Est, INSERM UMR 1033, 69372, Lyon Cedex 08, France

    A. Doublier

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  1. A. Doublier
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  2. D. Farlay
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  4. R. Vera
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  5. G. Boivin
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Corresponding author

Correspondence to A. Doublier.

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Doublier, A., Farlay, D., Jaurand, X. et al. Effects of strontium on the quality of bone apatite crystals: a paired biopsy study in postmenopausal osteoporotic women. Osteoporos Int 24, 1079–1087 (2013). https://doi.org/10.1007/s00198-012-2181-9

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  • DOI: https://doi.org/10.1007/s00198-012-2181-9

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