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Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density

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Abstract

Summary

The antiresorptive potency varies between different bisphosphonates. We investigated the effect of stopping oral bisphosphonate treatment for postmenopausal osteoporosis (ibandronate, alendronate, risedronate) on BTMs and BMD. After stopping treatment, all three groups showed an increase in BTMs and a decrease in hip BMD; however, none returned to pre-treatment baseline values.

Introduction

Bisphosphonates (BPs) continue to suppress bone turnover markers (BTMs) after treatment has stopped, leading to the suggestion that a pause in treatment could be considered for low-risk patients. Indirect comparisons suggest that after cessation of treatment, the effects on bone may differ between drugs. We investigated the effects of stopping oral BP treatments for postmenopausal osteoporosis on BTMs and bone mineral density (BMD).

Methods

We studied postmenopausal osteoporotic women who had previously taken part in a 2-year randomised study of three oral BPs (ibandronate, alendronate, or risedronate). At the end of the study, women with hip BMD T-score > − 2.5 and considered clinically appropriate to discontinue treatment were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs, and BMD was measured by dual-energy X-ray absorptiometry.

Results

All BTMs increased after treatment withdrawal but remained below the pre-treatment baseline with less suppression of BTMs for the risedronate group compared to alendronate and ibandronate up to 48 weeks. There was no difference between the BP groups 96 weeks after stopping treatment. The change in BMD during the 96 weeks after stopping treatment was − 1.6% (95% CI − 1.9 to − 1.2, P < 0.001) for the total hip and − 0.6% (95% CI − 1.1 to − 0.2, P = 0.17) at the lumbar spine with no difference between the three BP groups (P = 0.85 and P = 0.48, respectively).

Conclusion

For all treatment groups, there was an increase in BTMs and a decrease in hip BMD after stopping BPs for 2 years; however, none returned to pre-treatment baseline values.

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Acknowledgements

The TRIO study was funded by Warner-Chilcott, the bone turnover marker measurements were funded by Immunodiagnostics Systems. Professor Richard Eastell (Academic Unit of Bone Metabolism, The University of Sheffield) is a National Institute for Health Research (NIHR) Senior Investigator. The authors approved the manuscript for publication and vouched for the completeness and accuracy of the data. The funder was involved in the design, but not in the conduct, analysis or reporting of the study.

We are grateful to the data safety monitoring board, the Clinical Trials Research Unit, School of Health and Related Research, for data management and statistical support and the staff of the Academic Unit of Bone Metabolism for conducting the study. We would also like to acknowledge the Lay Advisory Panel for Bone Research and the participants of the study. We acknowledge the support of the NIHR Clinical Research Facility, Northern General Hospital, Sheffield. This work was supported by the South Yorkshire and North Derbyshire Musculoskeletal Biobank, which received ethics approval from NRES REC South Central Oxford C, (REC ref. 15/SC/0132) and is housed in the University of Sheffield Biorepository (HTA Licence no. 12182). The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR.

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Authors and Affiliations

  1. Academic Unit of Bone Metabolism, The Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK

    K. E. Naylor, M. A. Paggiosi, F. Gossiel, E. V. McCloskey, J. S. Walsh & R. Eastell

  2. Clinical Trials Research Unit, School of Health and Related Research, University of Sheffield, Sheffield, UK

    M. Bradburn

  3. Metabolic Bone Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital Sheffield, Sheffield, UK

    N. F. A. Peel

  4. Centre for Integrated Research into Musculoskeletal Ageing, Sheffield, UK

    E. V. McCloskey

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  1. K. E. Naylor
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Correspondence to K. E. Naylor.

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Conflicts of interest

NP has received speaker’s honoraria and funding to attend educational events from Warner-Chilcott, Eli Lilly, Amgen, GSK and Prostrakan and consultancy fees from Internis Pharma and Eli Lilly. JW has received speaker’s honoraria from Eli Lilly, grant funding from Alexion and Immunodiagnostic Systems, research drug and kits from Eli Lilly, Prostrakan (Kyowa Kirin), Consilient and Biomedica, consulting fees from Shire and Mereo Biopharma. EM has received speaker’s honoraria and/or research funding and/or advisory board funding from Warner-Chilcott, Merck, Amgen, GSK, Bayer, Consilient Healthcare, Hologic, Eli Lilly, Novartis, Pfizer, Servier, Wyeth and Roche. RE has received grant funding from Warner-Chilcott and the National Institute for Health Research (NIHR) and consultancy funding from Warner-Chilcott, Roche, Immunodiagnostic Systems and Merck. KN, MB, MP and FG have nothing to disclose.

Additional information

TRIO study

ClinicalTrials.gov number: NCT00666627, registered on 23rd April 2008

EudraCT: 2006–004738-33

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Naylor, K.E., Bradburn, M., Paggiosi, M.A. et al. Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density. Osteoporos Int 29, 1407–1417 (2018). https://doi.org/10.1007/s00198-018-4460-6

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  • DOI: https://doi.org/10.1007/s00198-018-4460-6

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