Abstract
Summary
In patients discontinuing ALN after a median of 7.0 years (range 5.0–20.0 years), BMD decreased, and bone turnover markers increased within the premenopausal reference range over 2 years. Increased p-CTX after 3 months was associated with greater bone loss at the hip confirming that maintenance of BMD is dependent on continued suppression of bone turnover.
Introduction
It is unknown how to monitor patients discontinuing alendronate (ALN) after more than 5 years. We investigated if BTM measured before or during treatment discontinuation with ALN predict bone loss after 1 or 2 years.
Methods
PROSA was a cohort study conducted at Aarhus University Hospital including postmenopausal women and men above 50 years treated with ALN ≥ 5 years who had osteopenia at the hip and BMD T-score at the lumbar spine > − 4. ALN was discontinued and BTMs were measured at baseline, months (M) 1, 3, 6, and 12, and DXA was performed at baseline, M6, and M12. We extended the study and measured BTMs and performed DXA at M24.
The primary endpoint was if changes in p-CTX at M3 or M6 predict changes in THBMD after 1 year (Clinicaltrials.gov: NCT03051620).
Results
We enrolled 136 participants discontinuing ALN after a median of 7.0 years (range 5.0–20.0 years) in PROSA and 124 participants in PROSA Extension. There was a significant decrease in LSBMD − 0.74% ± 0.27, THBMD − 2.65% ± 0.39, FNBMD − 2.35% ± 0.33, and trabecular bone score − 0.97% ± 0.35 and an increase in p-CTX by 61.1% ± 4.7 (p < 0.05 for all) after 24 months. Increase in p-CTX at M3 was associated with bone loss at the hip sites at M12 and M24.
Conclusion
In patients discontinuing ALN, BMD decreased significantly and BTMs increased within the reference range over 2 years. An increase in p-CTX after 3 months was associated with greater bone loss at the hip confirming that maintenance of BMD during treatment discontinuation is dependent on continued suppression of bone turnover.
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Data Availability
The study protocol is available in the appendix.
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Acknowledgments
We would like to thank all the participants for their extraordinary enthusiasm and cooperativeness throughout the study. Additionally, we would like to thank the foundations that supported the study financially.
Funding
The study was initiated by the investigators. The Foundation of Carl and Ellen Hertz, The Foundation of Aase and Ejnar Danielsen, The Svend Fælding Foundation, and Aarhus University have granted financial support. The funders of the study had no role in the study design, data collection, data interpretation, or writing of the report. The authors had full access to all the data and had final responsibility for the decision to submit for publication.
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All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare financial support from The Foundation of Carl and Ellen Hertz, The Foundation of Aase and Ejnar Danielsen, The Svend Fælding Foundation, and Aarhus University during the conduct of the study.
Additionally, Torben Harsløf received lecture fees from Amgen, Astra Zeneca, and Eli Lilly.
Bente Langdahl has received research funding to her institution from Amgen and Novo Nordisk. Bente Langdahl serves on advisory boards and speaker’s bureau for Eli Lilly, Amgen, UCB, Gedeon-Richter, and Gilead.
Niels Henrik Bruun and Anne Sophie Sølling have no additional competing interest.
Ethics approval
The Regional Ethics Committee (1-10-72-202-16), the Danish Data Protection Agency (1-16-02-485-16), the Danish Health and Medicines Authority (2016-0728-85), and The Danish Health Data Authority (FSEID-00003034) approved the study. The trial is registered at clinicaltrials.gov on 14 February 2017 (identifier NCT03346395). We conducted the study according to the Helsinki Declaration and the Danish Health Law.
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Sølling, A., Harsløf, T., Bruun, N. et al. The predictive value of bone turnover markers during discontinuation of alendronate: the PROSA study. Osteoporos Int 32, 1557–1566 (2021). https://doi.org/10.1007/s00198-021-05835-4
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DOI: https://doi.org/10.1007/s00198-021-05835-4