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The effect of prior bisphosphonate therapy on the subsequent therapeutic effects of strontium ranelate over 2 years

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Abstract

Summary

Many osteoporotic women prescribed strontium ranelate have previously received bisphosphonates. Prior bisphosphonate use blunted the spinal bone mineral density (BMD) response for 6 months. Hip BMD was blunted to a degree for 2 years, although there was an overall increase in hip BMD in contrast to the heel where BMD did not increase.

Introduction

Many osteoporotic women commenced on strontium ranelate have already received treatment with bisphosphonates. This study investigates whether prior bisphosphonate use impairs the subsequent therapeutic response to strontium ranelate.

Methods

Women were recruited who were either bisphosphonate naïve or currently receiving a bisphosphonate. All women received strontium ranelate and were followed up for 2 years.

Results

One hundred and twenty women were recruited. After 2 years, the bisphosphonate-naïve group had significant BMD increases of 8.9%, 6.0% and 6.4% at the spine, hip and heel, respectively. In the prior bisphosphonate group, BMD increased significantly at the spine (4.0%) and hip (2.5%) but not at the heel. At all time points at all sites, the BMD increase was greater in the bisphosphonate-naïve group. BMD at the spine did not increase during the first 6 months in the prior bisphosphonate group but then increased in parallel with the bisphosphonate-naïve group. In contrast, the difference between the two groups in hip BMD continued to increase throughout the 2 years. P1NP was suppressed in the prior bisphosphonate group for the first 6 months.

Conclusions

After bisphosphonate exposure, the BMD response to strontium ranelate is blunted for only 6 months at the spine. At the hip, a degree of blunting was observed over 2 years, although there was an overall increase in hip BMD in contrast to the heel where no increase in BMD was observed.

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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. 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 

  3. National Institute for Health and Clinical Excellence (2008) Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women. Available at: http://www.nice.org.uk/nicemedia/pdf/TA161quickrefguide.pdf

  4. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296:2927–2938

    Article  PubMed  CAS  Google Scholar 

  5. Middleton ET, Steel SA, Aye M, Doherty SM (2010) The effect of prior bisphosphonate therapy on the subsequent BMD and bone turnover response to strontium ranelate. J Bone Miner Res 25(3):455–462

    Article  PubMed  CAS  Google Scholar 

  6. 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(5):968–975

    PubMed  CAS  Google Scholar 

  7. Bruyère O, Collette J, Rizzoli R, Decock C, Ortolani S, Cormier C, Detilleux J, Reginster JY (2010) Relationship between 3-month changes in biochemical markers of bone remodelling and changes in bone mineral density and fracture incidence in patients treated with strontium ranelate for 3 years. Osteoporos Int 21(6):1031–1036

    Article  PubMed  Google Scholar 

  8. Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S, Audran M, Barker C, Anastasilakis AD, Fraser WD, Nickelsen T (2008) Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res 23(10):1591–1600

    Article  PubMed  CAS  Google Scholar 

  9. Ettinger B, San Martin J, Crans G, Pavo I (2004) Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 19(5):745–751

    Article  PubMed  CAS  Google Scholar 

  10. Middleton ET, Steel SA (2008) Routine versus targeted vertebral fracture assessment for the detection of vertebral fractures. Osteoporos Int 19(8):1167–1173

    Article  PubMed  CAS  Google Scholar 

  11. Blake GM, Preston N, Patel R, Herd RJ, Fogelman I (2000) Monitoring skeletal response to treatment which site to measure in the femur? J Clin Densitom 3:149–155

    Article  PubMed  CAS  Google Scholar 

  12. Steel SA, Thorpe J (2002) The GE-lunar prodigy: in vivo precision and cross-calibration. Calcif Tissue Int 71:277–278

    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(4):667–677

    Article  PubMed  CAS  Google Scholar 

  14. Nielsen SP, Slosman D, Sørensen 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(4):371–379

    Article  PubMed  CAS  Google Scholar 

  15. Bruyere O, Collette J, Reginster J-Y (2010) The effects of strontium ranelate on biochemical markers of bone turnover and their relationship with bone mineral density: reply to Stepan et al. Osteoporos Int 21(6):1039–1041

    Article  Google Scholar 

  16. Meunier PJ, Boivin G, Marie PJ (2009) About the comparison of two anabolic agents, teriparatide and strontium ranelate, in treated osteoporotic women. J Bone Miner Res 24(12):2066

    Article  PubMed  Google Scholar 

  17. Noble BS, Reeve J (2000) Osteocyte function, osteocyte death and bone fracture resistance. Mol Cell Endocrinol 159:7–13

    Article  PubMed  CAS  Google Scholar 

  18. Boivin G, Deloffre P, Perrat B (1996) Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S12911) administration. J Bone Miner Res 11:1302–1311

    Article  PubMed  CAS  Google Scholar 

  19. Liney GP, Bernard CP, Manton DJ, Turnbull LW, Langton CM (2007) Age, gender, and skeletal variation in bone marrow composition: a preliminary study at 3.0 Tesla. J Magn Reson Imaging 26:787–793

    Article  PubMed  Google Scholar 

  20. Rosen CJ, Bouxsein ML (2006) Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2:35–43

    Article  PubMed  CAS  Google Scholar 

  21. Busse B, Jobke B, Hahn M, Priemel M, Niecke M, Seitz S, Zustin J, Semler J, Amling M (2010) Effects of strontium ranelate administration on bisphosphonate-altered hydroxyapatite: matrix incorporation of strontium is accompanied by changes in mineralization and microstructure. Acta Biomater. doi:10.1016/j.actbio.2010.07.019

    PubMed  Google Scholar 

  22. Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San Martin J, Bone HG (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 25(1):72–81

    Article  PubMed  CAS  Google Scholar 

  23. Visekruna M, Wilson D, McKiernan FE (2008) Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab 93(8):2948–2952

    Article  PubMed  CAS  Google Scholar 

  24. Recker RR, Marin F, Ish-Shalom S, Möricke R, Hawkins F, Kapetanos G, de la Peña MP, Kekow J, Farrerons J, Sanz B, Oertel H, Stepan J (2009) Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Miner Res 24(8):1358–1368

    Article  PubMed  CAS  Google Scholar 

  25. Seibel MJ (2005) Biochemical markers of bone turnover: I. Biochemistry and variability. Clin Biochem Rev 26:97–122

    PubMed  Google Scholar 

  26. Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR (2009) High-dose oral vitamin D3 supplementation in the elderly. Osteoporos Int 20(8):1407–1415

    Article  PubMed  CAS  Google Scholar 

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Conflicts of interest

Servier Laboratories provided the strontium ranelate and a grant to fund the study. ProStrakan provided Adcal D3 as the calcium supplement but no financial support. Servier has paid speaker fees to Dr E Middleton (<£1,000) and Dr M Aye (<£2,000). All authors have no other conflicts of interest. The study design, the data collection, analysis and interpretation, and the manuscript were all carried out by the authors independent of Servier and ProStrakan.

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Authors and Affiliations

  1. Centre for Metabolic Bone Disease, Hull Royal Infirmary, Brocklehurst Building, 220-236 Anlaby Road, Hull, HU3 2RW, UK

    E. T. Middleton, S. A. Steel, M. Aye & S. M. Doherty

Authors
  1. E. T. Middleton
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  2. S. A. Steel
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  3. M. Aye
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  4. S. M. Doherty
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Correspondence to E. T. Middleton.

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Middleton, E.T., Steel, S.A., Aye, M. et al. The effect of prior bisphosphonate therapy on the subsequent therapeutic effects of strontium ranelate over 2 years. Osteoporos Int 23, 295–303 (2012). https://doi.org/10.1007/s00198-011-1547-8

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  • DOI: https://doi.org/10.1007/s00198-011-1547-8

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