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Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates

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Abstract

Summary

Transitioning postmenopausal women with osteoporosis from a bisphosphonate to denosumab appears to be safe and more effective at improving BMD than continuing treatment with a bisphosphonate.

Introduction

We conducted a patient-level pooled analysis of four studies to estimate the efficacy and safety of transitioning to denosumab vs. continuing bisphosphonate treatment in postmenopausal women who previously received oral bisphosphonates.

Methods

Patients received 60 mg denosumab once every 6 months or a bisphosphonate (oral alendronate, risedronate, ibandronate, or intravenous zoledronic acid). Endpoints were change from baseline in lumbar spine, total hip, femoral neck, and 1/3 radius BMD at month 12, change from baseline in serum CTX-1 and P1NP, and incidence of adverse events.

Results

A total of 2850 randomized patients (1424 bisphosphonate:1426 denosumab) were included in the analysis. Percentage change in BMD was significantly greater (p < 0.001) for denosumab vs. bisphosphonate at each skeletal site; differences in BMD changes ranged from 0.6 to 2.0%. Percentage decrease in serum CTX-1 and P1NP was significantly greater (p < 0.0001) for denosumab vs. bisphosphonate at months 1, 6, and 12; in the denosumab group only, percentage change in serum CTX-1 at month 1 was significantly correlated with percentage change in lumbar spine and total hip BMD at month 12. The incidences of adverse events were similar between treatment groups. Three patients (one bisphosphonate and two denosumab) had atypical femoral fractures, all from the denosumab vs. zoledronic acid study.

Conclusion

Postmenopausal women can safely transition from a bisphosphonate to denosumab, which is more effective at improving BMD than continuing with a bisphosphonate.

Clinical trials registration

NCT00377819, NCT00919711, NCT00936897, NCT01732770.

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Acknowledgments

Writing support was funded by Amgen Inc. and provided by Kathryn Boorer, PhD, of KB Scientific Communications, LLC.

Funding

This study was funded by Amgen Inc. P.M. has received grants/research support from Amgen, Eli Lilly, Merck, Radius Health, and Ultragenyx and consulting fees from Alexion, Amgen, Eli Lilly, Merck, Radius Health, and Ultragenyx. N.P., A.C., and S.H. are employees and shareholders of Amgen. C.W. was previously employed by Amgen. J.M.-S. has nothing to declare. A.S. has received consulting fees from Agnovos, Amgen, Eli Lilly, Merit, Radius, and UCB; is on the speakers’ bureau for Amgen, Eli Lilly, and Radius; and has a nonremunerative position of influence in the National Osteoporosis Foundation Board of Trustees. E.C. has received grants/research support from Amgen. H.G.B. has received grants/research support from Amgen, Merck, and Shire and consulting fees from Amgen, Grünenthal, Radius Health, and Merck, and is on the speakers’ bureau for Amgen, Radius Health, and Shire. W.L. has received consulting fees from and is on the speakers’ bureau for Amgen, Eli Lilly, Merck, UCB, and Curaphar. J.P.B. has received grants/research support from Amgen and Eli Lilly and consulting fees from Amgen, Eli Lilly, and Merck, and is on the speakers’ bureau for Amgen and Eli Lilly.

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Authors and Affiliations

  1. Colorado Center for Bone Research, 13991 Jubilee Trail, Pine, CO, 80470, USA

    P.D. Miller

  2. Amgen Inc., Thousand Oaks, CA, USA

    N. Pannacciulli, C. Wang, S. Huang & A. Chines

  3. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    J. Malouf-Sierra

  4. Georgetown University Medical Center, Washington, DC, USA

    A. Singer

  5. Krakow Medical Center, Krakow, Poland

    E. Czerwiński

  6. Michigan Bone and Mineral Clinic, Detroit, MI, USA

    H.G. Bone

  7. VU University Medical Center, Amsterdam, The Netherlands

    W. Lems

  8. CHU de Québec Research Centre and Laval University, QC, Québec, Canada

    J.P. Brown

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Correspondence to P.D. Miller.

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Informed consent was obtained from all individual participants included in each study.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Miller, P., Pannacciulli, N., Malouf-Sierra, J. et al. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int 31, 181–191 (2020). https://doi.org/10.1007/s00198-019-05233-x

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  • DOI: https://doi.org/10.1007/s00198-019-05233-x

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