Skip to main content

Advertisement

SpringerLink
Log in

Strontium ranelate does not stimulate bone formation in ovariectomized rats

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Introduction

Strontium ranelate (SrR) is suggested to function as a dual-acting agent in the treatment of postmenopausal osteoporosis with anti-resorptive and anabolic skeletal benefits. We evaluated the effects of SrR on the skeleton in ovariectomized (OVX) rats and evaluated the influence of dietary calcium.

Methods

Three-month old virgin female rats underwent ovariectomy (OVX, n = 50) or SHAM surgery (SHAM, n = 10). Four weeks post-surgery, rats were treated daily by oral gavage with distilled water (10 ml/kg/day) or SrR (25 or 150 mg/kg/day) for 90 days. Separate groups of animals for each dose of SrR were fed a low (0.1%) or normal (1.19%) calcium (Ca) diet. Static and dynamic histomorphometry, DXA, μ-CT, mechanical testing, and serum and skeletal concentrations of strontium were assessed.

Results

SrR at doses of 25 and 150 mg/kg/day did not increase bone formation on trabecular or periosteal bone surfaces, and failed to inhibit bone resorption of trabecular bone regardless of Ca intake. There were no improvements in bone mass, volume or strength with either dose of SrR given normal Ca.

Conclusion

These findings demonstrate that SrR at dosages of 25 and 150 mg/kg/day did not stimulate an anabolic bone response, and failed to improve the bone biomechanical properties of OVX rats.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Similar content being viewed by others

References

  1. McCaslin F, Janes J (1959) The effect of strontium lactate in the treatment of osteoporosis. Proc Mayo Clin 34:329–334

    Google Scholar 

  2. Shorr E, Carter AC (1952) The usefulness of strontium as an adjuvant to calcium in the remineralization of the skeleton in man. Bull Hosp Joint Dis 13:59–66

    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. Meunier PJ, Slosman DO, Delmas PD, Sebert JL, Brandi ML, Albanese C, Lorenc R, Pors-Nielsen S, De Vernejoul MC, Roces A, Reginster JY (2002) Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis–a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 87:2060–2066

    Article  PubMed  CAS  Google Scholar 

  5. 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 

  6. Roux C, Reginster JY, Fechtenbaum J, Kolta S, Sawicki A, Tulassay Z, Luisetto G, Padrino JM, Doyle D, Prince R, Fardellone P, Sorensen OH, Meunier PJ (2006) Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors. J Bone Miner Res 21:536–542

    Article  PubMed  CAS  Google Scholar 

  7. Seeman E, Vellas B, Benhamou C, Aquino JP, Semler J, Kaufman JM, Hoszowski K, Varela AR, Fiore C, Brixen K, Reginster JY, Boonen S (2006) Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in women eighty years of age and older. J Bone Miner Res 21:1113–1120

    Article  PubMed  CAS  Google Scholar 

  8. Burlet N, Reginster JY (2006) Strontium ranelate: the first dual acting treatment for postmenopausal osteoporosis. Clin Orthop Relat Res 443:55–60

    Article  PubMed  Google Scholar 

  9. Reginster JY, Sarlet N, Lejeune E, Leonori L (2005) Strontium ranelate: a new treatment for postmenopausal osteoporosis with a dual mode of action. Curr Osteoporos Rep 3:30–34

    Article  PubMed  Google Scholar 

  10. Seeman E (2007) Strontium ranelate. Osteoporosis, 3rd ed, Academic Press, pp 1767–1781

  11. Arlot M, Jiang Y, Genant H, Zhao J, Burt-Pichat B, Roux J, Delmas P, Meunier P (2007) Histomorphometric and micro-CT analysis of bone biospsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res 23:215–222

    Google Scholar 

  12. Barbara A, Delannoy P, Denis BG, Marie PJ (2004) Normal matrix mineralization induced by strontium ranelate in MC3T3-E1 osteogenic cells. Metabolism 53:532–537

    Article  PubMed  CAS  Google Scholar 

  13. Canalis E, Hott M, Deloffre P, Tsouderos Y, Marie PJ (1996) The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro. Bone 18:517–523

    Article  PubMed  CAS  Google Scholar 

  14. Takahashi N, Sasaki T, Tsouderos Y, Suda T (2003) S 12911-2 inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18:1082–1087

    Article  PubMed  CAS  Google Scholar 

  15. Baron R, Tsouderos Y (2002) In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation. Eur J Pharmacol 450:11–17

    Article  PubMed  CAS  Google Scholar 

  16. Bonnelye E, Chabadel A, Saltel F, Jurdic P (2007) Dual effect of strontium ranelate: Stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone 42:129–138

    Article  PubMed  CAS  Google Scholar 

  17. Verberckmoes SC, De Broe ME, D’Haese PC (2003) Dose-dependent effects of strontium on osteoblast function and mineralization. Kidney Int 64:534–543

    Article  PubMed  CAS  Google Scholar 

  18. Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 19:2012–2020

    Article  PubMed  CAS  Google Scholar 

  19. Marie PJ, Garba MT, Hott M, Miravet L (1985) Effect of low doses of stable strontium on bone metabolism in rats. Miner Electrolyte Metab 11:5–13

    PubMed  CAS  Google Scholar 

  20. Marie PJ, Hott M, Modrowski D, De Pollak C, Guillemain J, Deloffre P, Tsouderos Y (1993) An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 8:607–615

    PubMed  CAS  Google Scholar 

  21. Buehler J, Chappuis P, Saffar JL, Tsouderos Y, Vignery A (2001) Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis). Bone 29:176–179

    Article  PubMed  CAS  Google Scholar 

  22. Morohashi T, Sano T, Yamada S (1994) Effects of strontium on calcium metabolism in rats. I. A distinction between the pharmacological and toxic doses. Jpn J Pharmacol 64:155–162

    Article  PubMed  CAS  Google Scholar 

  23. Wronski TJ, Dann LM, Scott KS, Crooke LR (1989) Endocrine and pharmacological suppressors of bone turnover protect against osteopenia in ovariectomized rats. Endocrinology 125:810–816

    Article  PubMed  CAS  Google Scholar 

  24. Morohashi T, Sano T, Harai K, Yamada S (1995) Effects of strontium on calcium metabolism in rats. II. Strontium prevents the increased rate of bone turnover in ovariectomized rats. Jpn J Pharmacol 68:153–159

    Article  PubMed  CAS  Google Scholar 

  25. Ma YL, Bryant HU, Zeng Q, Schmidt A, Jee WS, Sato M (2005) Raloxifene and teriparatide (hPTH 1-34) have complementary effects on the osteopenic skeleton of ovariectomized rats. J Bone Miner Metab 23(Suppl):62–68

    PubMed  CAS  Google Scholar 

  26. Fox J, Miller MA, Newman MK, Metcalfe AF, Turner CH, Recker RR, Smith SY (2006) Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84) for 12 months reverses bone loss and enhances trabecular and cortical bone strength. Calcif Tissue Int 79:262–272

    Article  PubMed  CAS  Google Scholar 

  27. Boivin G, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14(Suppl 3):S19–S24

    PubMed  Google Scholar 

  28. Shahnazari M, Lang DH, Fosmire GJ, Sharkey NA, Mitchell AD, Leach RM (2007) Strontium administration in young chickens improves bone volume and architecture but does not enhance bone structural and material strength. Calcif Tissue Int

  29. Skoryna SC (1981) Effects of oral supplementation with stable strontium. Can Med Assoc J 125:703–712

    PubMed  CAS  Google Scholar 

  30. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610

    Article  PubMed  CAS  Google Scholar 

  31. Lanzirotti A, Miller L (2003) Imaging and microspectroscopy at the National Synchrotron Light Source. Synchr Rad News 15:17–26

    Google Scholar 

  32. Criss J (1977) NRLXRF, A FORTRAN program for X-ray fluorescence analysis. Naval Res Lab, Washington, DC

    Google Scholar 

  33. Heaney R (2002) Protein and calcium: antagonist or synergists. Am J Clin Nutr 75:609–610

    PubMed  CAS  Google Scholar 

  34. Sutton S, Bertsch PM, Newville M, Rivers M, Lanzirotti A (2002) Microfluorescence and microtomography analyses of heterogeneous earth and environmental materials. In reviews in mineralogy & geochemistry: applications of synchrotron radiation in low-temperature & environmental science. Mineralogical Society of America, Washington, DC, pp 429–483

    Google Scholar 

  35. Pors Nielsen S (2004) The biological role of strontium. Bone 35:583–588

    Article  PubMed  CAS  Google Scholar 

  36. 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

    PubMed  CAS  Google Scholar 

  37. Dahl SG, Allain P, Marie PJ, Mauras Y, Boivin G, Ammann P, Tsouderos Y, Delmas PD, Christiansen C (2001) Incorporation and distribution of strontium in bone. Bone 28:446–453

    Article  PubMed  CAS  Google Scholar 

  38. 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 

  39. Ozgur S, Sumer H, Kocoglu G (1996) Rickets and soil strontium. Arch Dis Child 75:524–526

    Article  PubMed  CAS  Google Scholar 

  40. Nielsen SP, Slosman D, Sorensen OH, Basse-Cathalinat B, De Cassin P, Roux CR, Meunier PJ (1999) Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. J Clin Densitom 2:371–379

    Article  PubMed  CAS  Google Scholar 

  41. Blake GM, Fogelman I (2007) Effect of bone strontium on BMD measurements. J Clin Densitom 10:34–38

    Article  PubMed  Google Scholar 

  42. Bonjour JP, Ammann P, Rizzoli R (1999) Importance of preclinical studies in the development of drugs for treatment of osteoporosis: a review related to the 1998 WHO guidelines. Osteoporos Int 9:379–393

    Article  PubMed  CAS  Google Scholar 

  43. WHO (1998) Guidelines for preclinical evaluation and clinical trials in osteoporosis. World Health Organization, Geneva

    Google Scholar 

Download references

Acknowledgements

We thank Lauren Waugh and Logan Vaught for their help in preparing the bone tissue for histological analysis and Antonio Lanzirotti for X-ray fluorescence data analysis. The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and Sanofi-Aventis) provided the strontium ranelate drug substance and financial support for the study. The study was also funded by an NIH Musculoskeletal Training Grant T32 AR-7581–09. The National Synchrotron Light Source is funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract No. DE-AC02–98CH10886. Portions of this work were performed at Beamline X26A, NSLS, Brookhaven National Laboratory, which is supported by the DOE-Basic Energy Sciences, Geosciences Division (DE-FG02–92ER14244 to the University of Chicago-CARS) and DOE-Office of Biological and Environmental Research, Environmental Remediation Sciences Division (DE-FC09–96-SR18546 to the University of Georgia).

Disclaimers/Funding Source

The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and Sanofi-Aventis), NIH Musculoskeletal Training Grant T32 AR-7581–09, National Synchrotron Light Source funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences (No. DE-AC02–98CH10886), Geosciences Division (No. DE-FG02–92ER14244 to the University of Chicago-CARS) and Department of Energy, Office of Biological and Environmental Research, Environmental Remediation Sciences Division (No. DE-FC09–96-SR18546 to the University of Georgia).

Author information

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    R. K. Fuchs, M. R. Allen, K. W. Condon, S. Reinwald & D. B. Burr

  2. Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN, USA

    R. K. Fuchs

  3. National Synchrotron Light Source, Brookhaven National Laboratory, Upton, NY, USA

    L. M. Miller

  4. Procter and Gamble Pharmaceuticals, Mason, OH, USA

    D. McClenathan, B. Keck & R. J. Phipps

  5. Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    D. B. Burr

Authors
  1. R. K. Fuchs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. R. Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. W. Condon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Reinwald
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. M. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. McClenathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B. Keck
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. J. Phipps
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D. B. Burr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. K. Fuchs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fuchs, R.K., Allen, M.R., Condon, K.W. et al. Strontium ranelate does not stimulate bone formation in ovariectomized rats. Osteoporos Int 19, 1331–1341 (2008). https://doi.org/10.1007/s00198-008-0602-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-008-0602-6

Keywords

Search

Navigation