Can bone turnover markers help to define the suitability and duration of bisphosphonate drug holidays?

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Abstract

Background: On stopping bisphosphonate treatment, bone resorption may increase before evidence of a decrease in bone density. Offset of bisphosphonate effect may therefore be monitored by measuring C-terminal telopeptide (CTX) following long-term bisphosphonate treatment to inform clinical decisions on drug holiday.

Methods: Retrospective analysis of 158 patients (83% female, mean age 71 years) starting a drug holiday had plasma CTX measured at discontinuation (baseline), n=138 and 4 months and n=136, and 12 months (n=100). Premenopausal mean CTX levels and the least significant change (LSC) detectable were used to define target thresholds for bone turnover.

Results: Following long-term bisphosphonate treatment (69% alendronic acid, 33% risedronate, mean duration 8 years SD 2.7), 32% patients had CTX above target (0.19 μg/L). In those with baseline CTX below threshold, 28% increased CTX to >0.19 μg/L and > LSC (0.06 μg/L) by 4 months (mean CTX increase 0.05 μg/L [95% confidence interval (CI): 0.04–0.06; p<0.0001]) and 53% by 12 months (mean CTX increase 0.09 μg/L [95% CI: 0.07–0.10; p<0.0001]), whilst 47% had no detectable changes in CTX over 12 months.

Conclusion: A third of patients showed inadequate suppression of CTX at baseline, despite long-term bisphosphonate treatment. Drug holiday may not be appropriate for this group, showing a poor therapeutic response or poor adherence. For more than a quarter of patients, bisphosphonate effects were wearing off at 4 months and around half by 12 months. We suggest CTX monitoring could identify those not experiencing a sustained bisphosphonate effect, including poorly adherence to therapy, and may be used during a drug holiday to prompt recommencement of therapy.

Keywords: diphosphonates, bone resorption, osteoporosis, bone remodelling, collagen type 1, risedronic acid, alendronate.

Citation: Statham L, Abdy S, Aspray TJ. Can bone turnover markers help to define the suitability and duration of bisphosphonate drug holidays? Drugs in Context 2020; 9: 2020-1-3. DOI: 10.7573/dic.2020-1-3

Contributions: LS, TJA, and SA designed the study. LS and SA collected data. LS wrote the research article with TJA by a process of iterative drafting. All authors reviewed the final manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: All authors declare that they have no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2020/04/dic.2020-1-3-COI.pdf

Acknowledgements: Study results were presented as an oral presentation and poster at ECTS conference. May 14, 2016.

Funding declaration: There was no funding received for this research or associated with the preparation of this article.

Copyright: Copyright © 2020 Statham L, Abdy S, Aspray TJ. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2020 Statham L, Abdy S, Aspray TJ. https://doi.org/10.7573/dic.2020-1-3. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://drugsincontext.com/can-bone-turnover-markers-help-to-define-the-suitability-and-duration-of-bisphosphonate-drug-holidays?

Correspondence: Louise Statham, The Bone Clinic, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK. Louise.statham@sunderland.ac.uk

Provenance: submitted; externally peer reviewed.

Submitted: 29 January 2020; Peer review comments to author: 1 April 2020; Revised manuscript received: 7 April 2020; Accepted: 7 April 2020; Publication date: 8 May 2020.

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