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Bone Mineral Density Changes After 1 Year of Denosumab Discontinuation in Postmenopausal Women with Long-Term Denosumab Treatment for Osteoporosis

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Abstract

The aim of the present study was to document the changes in bone mineral density (BMD) 1 year after denosumab loss-of-effect following long-term treatment with subcutaneous denosumab 60 mg Q6M during 7 or 10 years and in the absence of any treatment with a bone active substance. All postmenopausal women with osteoporosis who participated to the randomized placebo-controlled FREEDOM core trial and its open-label extension at the University Hospital of Bern, Switzerland, and who accepted to undergo off-treatment follow-up during 1 year after discontinuation, were included (N = 12). After 10 years of denosumab, mean lumbar spine (LS) BMD had increased by 21.2% vs. baseline. One year after discontinuation LS BMD had decreased by − 9.1% vs. Year 10, resulting in a net gain of 10.2% vs. baseline. At total hip (TH) and femoral neck (FN), BMD had increased by 8.3 and 8.1% in Year 10 vs. baseline, respectively. 1 Year after discontinuation, BMD had decreased by − 12.7 and − 11.0% vs. Year 10, respectively, corresponding to net BMD losses of − 5.5 and − 3.8% vs. baseline, respectively. Similar albeit less pronounced changes were observed in those treated with denosumab during 7 years. Stopping denosumab after long-term exposure resulted in BMD losses of large order of magnitude at all measured sites, suggesting that treatment duration may predict the rate and amount of bone lost.

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Acknowledgements

We are grateful to Philippe Kress, M.D., Glattbrugg, Switzerland, for his critical comments and review of the manuscript. Full access to source data was granted by Amgen Inc, Thousand Oaks, CA 91320, USA who did not sponsor the analysis and publication and had no influence on the results and contents of the manuscript. The authors have full control of all primary data and agree to allow the journal to review these data upon request.

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Authors and Affiliations

  1. Department of Osteoporosis, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland

    Albrecht Werner Popp, Nadshathra Varathan, Helene Buffat, Christoph Senn, Romain Perrelet & Kurt Lippuner

Authors
  1. Albrecht Werner Popp
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  2. Nadshathra Varathan
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  3. Helene Buffat
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  4. Christoph Senn
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  5. Romain Perrelet
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  6. Kurt Lippuner
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Contributions

Study design: AP and KL. Study conduct: AP and CS. Data collection: NV, RP, AP. Data analysis: AP and RP. Data interpretation: AP and KL. Drafting manuscript: AP. Revising manuscript content: AP, NV, HB, CS, RP, KL. Approving final version of manuscript: AP, NV, HB, CS, RP, KL. KL takes responsibility for the integrity of the data analysis.

Corresponding author

Correspondence to Kurt Lippuner.

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Conflict of interest

Kurt Lippuner is a primary investigator in clinical development programs in the field of osteoporosis from Amgen. Albrecht Popp and Christoph Senn are Sub-Investigators in clinical development programs in the field of osteoporosis from Amgen, Albrecht Popp has received personal fees for participation in advisory board meetings from Amgen Switzerland and Labatech Pharma. Nadshathra Varathan and Romain Perrelet declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This study was approved by the cantonal ethical review committee of Bern, Switzerland. All participants have provided their written informed consent. The study was carried out in accordance with the principles enunciated in the current version of the Declaration of Helsinki (DoH), the Essentials of Good Epidemiological Practice issued by Public Health Schweiz (EGEP), the Swiss Law and Swiss regulatory authority’s requirements as applicable.

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Popp, A.W., Varathan, N., Buffat, H. et al. Bone Mineral Density Changes After 1 Year of Denosumab Discontinuation in Postmenopausal Women with Long-Term Denosumab Treatment for Osteoporosis. Calcif Tissue Int 103, 50–54 (2018). https://doi.org/10.1007/s00223-018-0394-4

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  • DOI: https://doi.org/10.1007/s00223-018-0394-4

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