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Effect of raloxifene after recombinant teriparatide [hPTH(1–34)] treatment in postmenopausal women with osteoporosis

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Abstract

Summary

Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment.

Introduction

We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide.

Methods

Following a year of open-label teriparatide 20 μg/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry.

Results

The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (−1.0 ± 0.3%, P = 0.004; and −4.0 ± 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (−2.6 ± 0.4% (raloxifene-raloxifene) and −2.7 ± 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 ± 0.5% vs. 5.1 ± 0.5%; FN: 3.4 ± 0.6% vs. 3.0 ± 0.5%).

Conclusion

Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment.

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Acknowledgments

In addition to the authors, the following principal investigators participated in the study. Australia: P. Nash, E. Romas, P. Sambrook, E. Seeman; Canada: A.B. Hodsman, D.A. Hanley, R. Faraawi, R. Dumas, W.P. Olszynski; France: P. Delmas, M.C. De Vernejoul, P. Fardellone, G. Weryha; Italy: V. Lo Cascio, G.C. Isaia, P. Filipponi; Spain: M. Nolla, N. Guanabens, J.J. Gomez-Reino, C. Lozano-Tonkin, F. Escobar, E. Collantes, G. Herrero-Beaumont; United States: P. Camacho, W.H. Utian.

We thank Melinda Rance and Mary Ellen Perron for technical assistance and preparation of the figures.

Funding

Drs. Li Xie, Gail P. Dalsky, and Adrien Sipos are full-time employees of Eli Lilly and Company. Dr. Javier San Martin was an employee of Eli Lilly and Company at the time the study was done. This study was funded by Lilly Research Laboratories, Eli Lilly and Company, Indianapolis IN.

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Author notes

  1. J. San Martin

    Present address: Global Development Leader Bone Therapeutic Area A, One Amgen Center Drive 27-5-A, Thousand Oaks, CA, 91320, USA

Authors and Affiliations

  1. Riabilitazione Reumatologica, University of Verona, Valeggio s/Mincio, Verona, Italy

    S. Adami

  2. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA

    J. San Martin, L. Xie, G. P. Dalsky & A. Sipos

  3. Unidad de Metabolismo Óseo, Hospital Universitario San Cecilio, Granada, Spain

    M. Muñoz-Torres

  4. Division of Endocrinology & Metabolism, Indiana University School of Medicine, 541 N. Clinical Dr., CL 459, Indianapolis, IN, 46202-5111, USA

    M. J. Econs

  5. Oregon Osteoporosis Center, 5050 NE Hoyt Street, Suite #651, Portland, OR, 97213, USA

    M. McClung

  6. Charité – Universitätsmedizin, Campus Benjamin Franklin, Berlin, Germany

    D. Felsenberg

  7. Groupe de recherche en rhumatologie et maladies osseuses, S-784, 2705 Boul. Laurier, Québec, Québec, G1V 4G2, Canada

    J. P. Brown

  8. Ospedale Di Careggi, Firenze, Italy

    M. L. Brandi

  9. University of Florence, Viale Pieraccini, 6, Florence, 50139, Italy

    M. L. Brandi

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  1. S. Adami
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Correspondence to S. Adami.

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Adami, S., San Martin, J., Muñoz-Torres, M. et al. Effect of raloxifene after recombinant teriparatide [hPTH(1–34)] treatment in postmenopausal women with osteoporosis. Osteoporos Int 19, 87–94 (2008). https://doi.org/10.1007/s00198-007-0485-y

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  • DOI: https://doi.org/10.1007/s00198-007-0485-y

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