Skip to main content

Advertisement

Log in

The effect of PTH(1–84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: results of a randomized, open-label clinical trial

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

Abstract

Summary

We explored the effects of PTH(1–84) compared with strontium ranelate on bone remodeling as measured by bone remodeling markers in postmenopausal women with osteoporosis. Biochemical markers of bone formation were significantly increased after treatment with PTH(1–84) but not strontium ranelate, indicating a different mechanism of action between these agents.

Introduction

PTH(1–84) and strontium ranelate (SR) are both known to reduce fracture risk in osteoporosis. Measuring changes in biochemical markers of bone turnover induced by these agents can help in characterizing the action of PTH(1–84) and SR on bone remodeling.

Methods

A 24-week, randomized, open-label, parallel group, phase IV trial was conducted in 81 postmenopausal women with primary osteoporosis (≥50 years of age, lumbar spine, or total hip T-score ≤−2.5 SD) to assess the effect of SR as compared to PTH(1–84) on bone formation markers P1NP and BSAP. The bone resorption marker CTX was also measured. Subjects were randomly assigned to receive daily either 100 μg PTH(1–84) (n = 41) (subcutaneous injection) or oral 2 g SR (n = 40) for 24 weeks with daily supplements of 800 IU vitamin D3 and 1,000 mg calcium. Patient-reported outcomes were collected to investigate the effect of treatment on quality of life (QoL).

Results

Percentage changes from baseline in P1NP and BSAP were significantly increased for PTH(1–84) by week 24 compared with SR (p < 0.0001). Significant changes from baseline in P1NP and BSAP were noted for PTH(1–84) from week 4 onwards; no significant changes were noted for SR. A trend towards a positive impact on QoL was seen with PTH(1–84) treatment. Safety profiles concur with previous analyses.

Conclusions

PTH(1–84) had a more rapid and higher effect on bone formation markers compared to SR, indicating that SR has a different mode of action on bone remodeling than the bone building agent PTH(1–84) in postmenopausal women with osteoporosis.

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

Access this article

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
Fig. 5

Similar content being viewed by others

References

  1. Delaney MF (2006) Strategies for the prevention and treatment of osteoporosis during early postmenopause. Am J Obstet Gynecol 194:S12–S23

    Article  PubMed  Google Scholar 

  2. Johnell O, Oden A, De Laet C, Garnero P, Delmas PD, Kanis JA (2002) Biochemical indices of bone turnover and the assessment of fracture probability. Osteoporos Int 13:523–526

    Article  PubMed  CAS  Google Scholar 

  3. Singer FR, Eyre DR (2008) Using biochemical markers of bone turnover in clinical practice. Cleve Clin J Med 75:739–750

    Article  PubMed  Google Scholar 

  4. Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of scientific advisors of the international osteoporosis foundation. Osteoporos Int 11:S2–S17

    Article  PubMed  Google Scholar 

  5. Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, Lang TF, McGowan JA, Rosen CJ (2005) One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N Engl J Med 353:555–565

    Article  PubMed  CAS  Google Scholar 

  6. Greenspan SL, Bone HG, Ettinger MP, Hanley DA, Lindsay R, Zanchetta JR, Blosch CM, Mathisen AL, Morris SA, Marriott TB (2007) Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med 146:326–339

    PubMed  Google Scholar 

  7. Recker RR, Bare SP, Smith SY, Varela A, Miller MA, Morris SA, Fox J (2009) Cancellous and cortical bone architecture and turnover at the iliac crest of postmenopausal osteoporotic women treated with parathyroid hormone 1–84. Bone 44:113–119

    Article  PubMed  CAS  Google Scholar 

  8. Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ (2003) The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 349:1207–1215

    Article  PubMed  CAS  Google Scholar 

  9. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441

    Article  PubMed  CAS  Google Scholar 

  10. Chen P, Satterwhite JH, Licata AA, Lewiecki EM, Sipos AA, Misurski DM, Wagman RB (2005) Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 20:962–970

    Article  PubMed  CAS  Google Scholar 

  11. 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 

  12. Marie PJ (2005) Strontium ranelate: a novel mode of action optimizing bone formation and resorption. Osteoporos Int 16:S7–S10

    Article  PubMed  CAS  Google Scholar 

  13. Matsumoto A (1988) Effect of strontium chloride on bone resorption induced by prostaglandin E2 in cultured bone. Arch Toxicol 62:240–241

    Article  PubMed  CAS  Google Scholar 

  14. 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 

  15. 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 

  16. Marie PJ, Hott M, Modrowski D, De PC, 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

    Article  PubMed  CAS  Google Scholar 

  17. Bilezikian JP (2008) Combination anabolic and antiresorptive therapy for osteoporosis: opening the anabolic window. Curr Osteoporos Rep 6:24–30

    Article  PubMed  Google Scholar 

  18. Recker RR, Marin F, Ish-Shalom S, Moricke R, Hawkins F, Kapetanos G, de la Pena 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 24:1358–1368

    Article  PubMed  CAS  Google Scholar 

  19. 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 

  20. Ferrari S (2010) Comparing and contrasting the effects of strontium ranelate and other osteoporosis drugs on microarchitecture. Osteoporos Int 21:S437–S442

    Article  PubMed  CAS  Google Scholar 

  21. Blake GM, Compston JE, Fogelman I (2009) Commentary: could strontium ranelate have a synergistic role in the treatment of osteoporosis? J Bone Miner Res 24:1354–1357

    Article  PubMed  CAS  Google Scholar 

  22. Ostelo RW, Deyo RA, Stratford P, Waddell G, Croft P, Von KM, Bouter LM, de Vet HC (2008) Interpreting change scores for pain and functional status in low back pain: towards international consensus regarding minimal important change. Spine Phila Pa 1976 33:90–94

    Article  PubMed  Google Scholar 

  23. Weisman SM, Matkovic V (2005) Potential use of biochemical markers of bone turnover for assessing the effect of calcium supplementation and predicting future fracture risk. Clin Ther 27:299–308

    Article  PubMed  CAS  Google Scholar 

  24. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 340:c869

    Article  PubMed  Google Scholar 

  25. Schulz KF, Altman DG, Moher D (2010) CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMC Med 8:18

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all the investigators involved in the study. Editorial assistance with this manuscript was provided by Carol A Richter, PhD, ApotheCom ScopeMedical Ltd. The study and editorial assistance were funded by Nycomed. The manuscript has been developed in accordance with CONSORT 2010 guidelines [24, 25].

Conflicts of interest

José Manuel Quesada-Gómez, Christian Muschitz and Juan Gómez-Reino report no potential conflict of interest relevant for this article. Hans Peter Dimai has received speaking fees, consulting fees, and/or payment for advisory board services, and grant support from both Servier and Nycomed. Hanna Greisen and Henrik Steen Andersen are formal employees of Nycomed.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. Greisen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Quesada-Gómez, J.M., Muschitz, C., Gómez-Reino, J. et al. The effect of PTH(1–84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: results of a randomized, open-label clinical trial. Osteoporos Int 22, 2529–2537 (2011). https://doi.org/10.1007/s00198-010-1460-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-010-1460-6

Keywords

Navigation