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

Lookup NU author(s): Dr Terry Aspray



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


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. 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.

Publication metadata

Author(s): Statham L, Abdy S, Aspray TJ

Publication type: Article

Publication status: Published

Journal: Drugs in Context

Year: 2020

Volume: 9

Online publication date: 08/05/2020

Acceptance date: 07/04/2020

Date deposited: 16/10/2020

ISSN (print): 1745-1981

ISSN (electronic): 1740-4398

Publisher: Bioexcel Publishing LTD


DOI: 10.7573/DIC.2020-1-3


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