Skip to main content

Advertisement

Log in

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis

Results of a 2-year study

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

Abstract

Summary

Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2 years, in postmenopausal osteoporotic women.

Introduction

Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk.

Methods

Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers.

Results

In the intention-to-treat population (n = 83, age: 64 ± 8 years; lumbar T-score: −2.8 ± 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (−0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (−1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated.

Conclusions

Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.

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

Access this article

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Bouxsein ML, Seeman E (2009) Quantifying the material and structural determinants of bone strength. Best Pract Res Clin Rheumatol 23(6):741–753

    Article  PubMed  Google Scholar 

  2. Seeman E, Delmas PD (2006) Bone quality–the material and structural basis of bone strength and fragility. N Engl J Med 354(21):2250–2261

    Article  PubMed  CAS  Google Scholar 

  3. Griffith JF, Genant HK (2008) Bone mass and architecture determination: state of the art. Best Pract Res Clin Endocrinol Metab 22(5):737–764

    Article  PubMed  Google Scholar 

  4. Adams JE (2009) Quantitative computed tomography. Eur J Radiol 71(3):415–424

    Article  PubMed  Google Scholar 

  5. Laib A, Ruegsegger P (1999) Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-micron-resolution microcomputed tomography. Bone 24(1):35–39

    Article  PubMed  CAS  Google Scholar 

  6. MacNeil JA, Boyd SK (2007) Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys 29(10):1096–1105

    Article  PubMed  Google Scholar 

  7. Vico L, Zouch M, Amirouche A, Frere D, Laroche N, Koller B et al (2007) High-resolution pQCT analysis at the distal radius and tibia discriminates patients with recent wrist and femoral neck fractures. J Bone Miner Res 23(11):1741–1750

    Article  Google Scholar 

  8. Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD (2007) Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res 22(3):425–433

    Article  PubMed  Google Scholar 

  9. Sornay-Rendu E, Cabrera-Bravo JL, Boutroy S, Munoz F, Delmas PD (2009) Severity of vertebral fractures is associated with alterations of cortical architecture in postmenopausal women. J Bone Miner Res 24(4):737–743

    Article  PubMed  Google Scholar 

  10. Sornay-Rendu E, Boutroy S, Munoz F, Bouxsein ML (2009) Cortical and trabecular architecture are altered in postmenopausal women with fractures. Osteoporos Int 20(8):1291–1297

    Article  PubMed  CAS  Google Scholar 

  11. Boutroy S, Bouxsein ML, Munoz F, Delmas PD (2005) In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab 90(12):6508–6515

    Article  PubMed  CAS  Google Scholar 

  12. MacNeil JA, Boyd SK (2007) Load distribution and the predictive power of morphological indices in the distal radius and tibia by high resolution peripheral quantitative computed tomography. Bone 41(1):129–137

    Article  PubMed  Google Scholar 

  13. Pistoia W, Van Rietbergen B, Lochmuller EM, Lill CA, Eckstein F, Ruegsegger P (2002) Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone 30(6):842–848

    Article  PubMed  CAS  Google Scholar 

  14. MacNeil JA, Boyd SK (2008) Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone 42(6):1203–1213

    Article  PubMed  Google Scholar 

  15. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD et al (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350(5):459–468

    Article  PubMed  CAS  Google Scholar 

  16. Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C et al (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(5):2816–2822

    Article  PubMed  CAS  Google Scholar 

  17. Arlot ME, Jiang Y, Genant HK, Zhao J, Burt-Pichat B, Roux JP et al (2008) Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res 23(2):215–222

    Article  PubMed  CAS  Google Scholar 

  18. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348(9041):1535–1541

    Article  PubMed  CAS  Google Scholar 

  19. Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ (1997) Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest 100(6):1475–1480

    Article  PubMed  CAS  Google Scholar 

  20. Rizzoli R, Laroche M, Krieg MA, Frieling I, Thomas T, Delmas P et al (2010) Strontium ranelate and alendronate have differing effects on distal tibia bone microstructure in women with osteoporosis. Rheumatol Int 30(10):1341–1348

    Article  PubMed  CAS  Google Scholar 

  21. Laib A, Hildebrand T, Hauselmann HJ, Ruegsegger P (1997) Ridge number density: a new parameter for in vivo bone structure analysis. Bone 21(6):541–546

    Article  PubMed  CAS  Google Scholar 

  22. Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS (1983) Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest 72(4):1396–1409

    Article  PubMed  CAS  Google Scholar 

  23. Burghardt AJ, Kazakia GJ, Ramachandran S, Link TM, Majumdar S (2010) Age- and gender-related differences in the geometric properties and biomechanical significance of intracortical porosity in the distal radius and tibia. J Bone Miner Res 25(5):983–993

    PubMed  Google Scholar 

  24. Nishiyama KK, Macdonald HM, Buie HR, Hanley DA, Boyd SK (2010) Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study. J Bone Miner Res 25(4):882–890

    PubMed  Google Scholar 

  25. Van Rietbergen B, Weinans H, Huiskes R, Odgaard A (1995) A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech 28(1):69–81

    Article  PubMed  Google Scholar 

  26. Homminga J, Huiskes R, Van Rietbergen B, Ruegsegger P, Weinans H (2001) Introduction and evaluation of a gray-value voxel conversion technique. J Biomech 34(4):513–517

    Article  PubMed  CAS  Google Scholar 

  27. Turner CH, Rho J, Takano Y, Tsui TY, Pharr GM (1999) The elastic properties of trabecular and cortical bone tissues are similar: results from two microscopic measurement techniques. J Biomech 32(4):437–441

    Article  PubMed  CAS  Google Scholar 

  28. Turner CH, Burr DB (1993) Basic biomechanical measurements of bone: a tutorial. Bone 14(4):595–608

    Article  PubMed  CAS  Google Scholar 

  29. Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ (2000) Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27(5):687–694

    Article  PubMed  CAS  Google Scholar 

  30. 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(4):667–677

    Google Scholar 

  31. Lewiecki EM, Keaveny TM, Kopperdahl DL, Genant HK, Engelke K, Fuerst T et al (2009) Once-monthly oral ibandronate improves biomechanical determinants of bone strength in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 94(1):171–180

    Article  PubMed  CAS  Google Scholar 

  32. Busse B, Jobke B, Hahn M, Priemel M, Niecke M, Seitz S et al (2010) Effects of strontium ranelate administration on bisphosphonate-altered hydroxyapatite: matrix incorporation of strontium is accompanied by changes in mineralization and microstructure. Acta Biomater 6(12):4513–4521

    Article  PubMed  CAS  Google Scholar 

  33. Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S (2010) A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J Bone Miner Res 25(12):2558–2571

    Article  PubMed  Google Scholar 

  34. Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E et al (2010) Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 25(8):1886–1894

    Article  PubMed  Google Scholar 

  35. Macdonald HM, Nishiyama KK, Hanley DA, Boyd SK (2011) Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Osteoporos Int 22(1):357–362

    Article  PubMed  CAS  Google Scholar 

  36. Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L et al (2001) Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res 16(10):1846–1853

    Article  PubMed  CAS  Google Scholar 

  37. Hodsman AB, Kisiel M, Adachi JD, Fraher LJ, Watson PH (2000) Histomorphometric evidence for increased bone turnover without change in cortical thickness or porosity after 2 years of cyclical hPTH(1–34) therapy in women with severe osteoporosis. Bone 27(2):311–318

    Article  PubMed  CAS  Google Scholar 

  38. Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF (2003) Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res 18(11):1932–1941

    Article  PubMed  CAS  Google Scholar 

  39. Zebaze RM, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI et al (2010) Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet 375(9727):1729–1736

    Article  PubMed  Google Scholar 

  40. Burr DB (2010) Cortical bone: a target for fracture prevention? Lancet 375(9727):1672–1673

    Article  PubMed  Google Scholar 

  41. Boyd SK, Szabo E, Ammann P (2011) Increased bone strength is associated with improved bone microarchitecture in intact female rats treated with strontium ranelate: a finite element analysis study. Bone 48(5):1109–1116

    Article  PubMed  CAS  Google Scholar 

  42. Bruyere O, Roux C, Detilleux J, Slosman DO, Spector TD, Fardellone P et al (2007) Relationship between bone mineral density changes and fracture risk reduction in patients treated with strontium ranelate. J Clin Endocrinol Metab 92(8):3076–3081

    Article  PubMed  CAS  Google Scholar 

  43. Vilayphiou N, Boutroy S, Sornay-Rendu E, Van Rietbergen B, Munoz F, Delmas PD et al (2010) Finite element analysis performed on radius and tibia HR-pQCT images and fragility fractures at all sites in postmenopausal women. Bone 46(4):1030–1037

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The study was sponsored by Servier.

Conflicts of interest

All authors are investigators in the study, except A. Laib, who was responsible for central reading of HR-pQCT parameters, and S. Boutroy, who was responsible for central reading of FEA parameters.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Rizzoli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rizzoli, R., Chapurlat, R.D., Laroche, JM. et al. Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Osteoporos Int 23, 305–315 (2012). https://doi.org/10.1007/s00198-011-1758-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-011-1758-z

Keywords

Navigation