Skip to main content

Advertisement

SpringerLink
Log in

Effect of prior and ongoing raloxifene therapy on response to PTH and maintenance of BMD after PTH therapy

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

Abstract

Summary

Women with osteoporosis on raloxifene were randomized to 1-34hPTH + raloxifene or raloxifene alone for one year. In the PTH + raloxifene group, bone turnover increased 125–584%, spine BMD increased 9.6%, hip BMD increased 1.2–3.6% and radius BMD declined 4.3%. During the follow-up year, on continued raloxifene, BMD declined slightly at all sites except the femoral neck.

Introduction

The influence of prior antiresorptives on response to 1–34PTH and the ability to maintain BMD gains might differ for antiresorptive agents with different potencies. The objectives were to evaluate biochemical and bone density responses to 1–34PTH in patients on prior and ongoing raloxifene and to determine whether raloxifene maintains bone gains.

Methods

Forty-two postmenopausal women with osteoporosis on raloxifene were randomized to raloxifene alone or 1–34PTH daily for 12 months (continuing raloxifene). Women were then followed for 12 months on raloxifene alone. Bone turnover markers and BMD were measured at baseline and at 3, 6, 12, 18 and 24 months.

Results

Biochemical indices increased rapidly during PTH treatment with peak increments of 125–584% for the three markers (p < 0.001 vs. baseline). After one year of PTH, mean BMD increases were 9.6% for spine, 2.7% for total hip, 3.6% for trochanter (all p < 0.005) and 1.2% in femoral neck (NS), while BMD declined 4.3% in the radius (p = 0.003). After PTH withdrawal, on continued raloxifene, BMD declined slightly (0.7–2.9% losses; NS) at all sites, except the femoral neck, where BMD increased modestly (p = 0.04). At 24 months, spine and femoral neck BMD remained significantly higher than baseline, while radius BMD remained significantly lower (all p < 0.04).

Conclusion

Substantial gains in BMD of the spine and hip, but not the radius, are seen with one year of PTH treatment in patients on prior raloxifene. After PTH is discontinued, raloxifene partially maintains PTH-induced BMD gains in the spine and hip.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF (2005) Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med 165:1762–1768

    Article  PubMed  CAS  Google Scholar 

  2. Cosman F, Nieves J, Woelfert L, Formica C, Gordon S, Shen V, Lindsay R (2001) Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res 16:925–931

    Article  PubMed  CAS  Google Scholar 

  3. Lindsay R, Cosman F, Zhou H, Bostrom MP, Shen VW, Cruz JD, Nieves JW, Dempster DW (2006) A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J Bone Miner Res 21:366–373

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R (2005) Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med 353:566–575

    Article  PubMed  CAS  Google Scholar 

  6. 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 

  7. Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, Glass EV, Myers SL, Krege JH (2005) Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res 20:1905–1911

    Article  PubMed  CAS  Google Scholar 

  8. 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 19:745–751

    Article  PubMed  CAS  Google Scholar 

  9. Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM (2003) The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 349:1216–1226

    Article  PubMed  CAS  Google Scholar 

  10. Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F (1997) Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 350:550–555

    Article  PubMed  CAS  Google Scholar 

  11. Lindsay R, Scheele WH, Neer R, Pohl G, Adami S, Mautalen C, Reginster JY, Stepan JJ, Myers SL, Mitlak BH (2004) Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med 164:2024–2030

    Article  PubMed  Google Scholar 

  12. 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 

  13. Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP (2000) Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 85:3069–3076

    Article  PubMed  CAS  Google Scholar 

  14. Riggs BL, Wahner HW, Dunn WL, Mazess RB, Offord KP, Melton LJ, 3rd (1981) Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest 67:328–335

    Article  PubMed  CAS  Google Scholar 

  15. Burr DB, Hirano T, Turner CH, Hotchkiss C, Brommage R, Hock JM (2001) Intermittently administered human parathyroid hormone(1–34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys. J Bone Miner Res 16:157–165

    Article  PubMed  CAS  Google Scholar 

  16. Allen MR, Burr DB (2006) Parathyroid hormone and bone biomechanics. Clinical Reviews in Bone and Mineral Metabolism 4:259–268

    Article  CAS  Google Scholar 

  17. Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB (2007) Effects of a One-Month Treatment with Parathyroid Hormone (1–34) on Bone Formation on Cancellous, Endocortical and Periosteal Surfaces of the Human Ilium. J Bone Miner Res 22:495–502

    Google Scholar 

  18. Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R (2003) Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 88:1150–1156

    Article  PubMed  CAS  Google Scholar 

  19. Zanchetta JR, Bogado CE, Ferretti JL, Wang O, Wilson MG, Sato M, Gaich GA, Dalsky GP, Myers SL (2003) Effects of teriparatide [recombinant human parathyroid hormone (1–34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 18:539–543

    Article  PubMed  CAS  Google Scholar 

  20. Uusi-Rasi K, Semanick LM, Zanchetta JR, Bogado CE, Eriksen EF, Sato M, Beck TJ (2005) Effects of teriparatide [rhPTH (1–34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women. Bone 36:948–958

    Article  PubMed  CAS  Google Scholar 

  21. Iida-Klein A, Zhou H, Lu SS, Levine LR, Ducayen-Knowles M, Dempster DW, Nieves J, Lindsay R (2002) Anabolic action of parathyroid hormone is skeletal site specific at the tissue and cellular levels in mice. J Bone Miner Res 17:808–816

    Article  PubMed  CAS  Google Scholar 

  22. Ma Y, Jee WS, Yuan Z, Wei W, Chen H, Pun S, Liang H, Lin C (1999) Parathyroid hormone and mechanical usage have a synergistic effect in rat tibial diaphyseal cortical bone. J Bone Miner Res 14:439–448

    Article  PubMed  CAS  Google Scholar 

  23. Kim CH, Takai E, Zhou H, von Stechow D, Muller R, Dempster DW, Guo XE (2003) Trabecular bone response to mechanical and parathyroid hormone stimulation: the role of mechanical microenvironment. J Bone Miner Res 18:2116–2125

    Article  PubMed  CAS  Google Scholar 

  24. Lindsay R, Cosman F, Zhou H, Nieves J, Bostrom MP, Barbuto N, Dempster D (2007) Prior alendronate treatment does not inhibit the early estimulation of osteoblast activity in response to teriparatide. JBMR 22 (Supp 1): Abstract

  25. Ma YL, Bryant HU, Zeng Q, Schmidt A, Hoover J, Cole HW, Yao W, Jee WS, Sato M (2003) New bone formation with teriparatide [human parathyroid hormone-(1–34)] is not retarded by long-term pretreatment with alendronate, estrogen, or raloxifene in ovariectomized rats. Endocrinology 144:2008–2015

    Article  PubMed  CAS  Google Scholar 

  26. Cosman F, Wermers RA, Recknor C, Mauck KF, Xie L, Glass EV, Krege JH (2007) Efiicacy of adding teriparatide versus switching to teriparatide in postmenopausal women with osteoporosis previously treated with raloxifene or alendronate. JBMR 22 (Supp 1): Abstract 0423

Download references

Author information

Authors and Affiliations

  1. Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, 10993, USA

    F. Cosman, J. W. Nieves, M. Zion, N. Barbuto & R. Lindsay

  2. Department of Medicine, Columbia University, New York, NY, 10032, USA

    F. Cosman & R. Lindsay

  3. Department of Epidemiology, Columbia University, New York, NY, 10032, USA

    J. W. Nieves

  4. Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, 10993, USA

    F. Cosman

Authors
  1. F. Cosman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. W. Nieves
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Zion
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Barbuto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Lindsay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Cosman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cosman, F., Nieves, J.W., Zion, M. et al. Effect of prior and ongoing raloxifene therapy on response to PTH and maintenance of BMD after PTH therapy. Osteoporos Int 19, 529–535 (2008). https://doi.org/10.1007/s00198-007-0475-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-007-0475-0

Keywords

Search

Navigation