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Fracture rates in patients discontinuing alendronate treatment in real life: a population-based cohort study

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Abstract

Summary

In this nationwide register-based cohort study, we found no difference in the risk of fractures in patients discontinuing versus continuing alendronate (ALN) treatment after 5 years.

Introduction

Information on fracture risk in patients discontinuing ALN in a real-life setting is sparse. We aimed to examine ALN discontinuation patterns, compare fracture rates in patients discontinuing versus continuing ALN after 5 years of treatment, and define determinants of fractures in ALN discontinuers.

Methods

A nationwide population-based cohort study using Danish health registry data. Our source population was individuals who had redeemed ≥ 2 ALN prescriptions between January 1, 1995, and September 1, 2017.

Results

We found that 25% of all ALN initiators used ALN for less than 1 year and 43% continued treatment for at least 5 years. We classified n = 1865 as ALN discontinuers and n = 29,619 as ALN continuers. Using Cox proportional hazards regression analysis and an “as-treated” approach, we observed no increased risk of any fracture (incidence rate ratio (IRR) 1.06, 95% CI 0.92–1.23), vertebral fracture (IRR 0.59, 95% CI 0.33–1.05), hip fracture (IRR 1.04, 95% CI 0.75–1.45), or major osteoporotic fracture (IRR 1.05, 95% CI 0.88–1.25) in the ALN discontinuers compared to continuers during a follow-up time of 1.84 ± 1.56 years (mean ± SD) and 2.51 ± 1.60 years, respectively. ALN re-initiation was a major determinant of follow-up among the discontinuers. Old age (> 80 vs. 50–60 years, unadjusted IRR 2.92, 95% CI 1.18–7.24) was the strongest determinant for fractures following ALN discontinuation.

Conclusion

In a real-world setting, less than 50% continued ALN treatment for 5 years. We found no difference in the risk of fractures in patients discontinuing versus continuing ALN after 5 years.

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Data availability

The study protocol will be available following publication to investigators who provide a methodologically sound proposal to the corresponding author.

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Funding

The study was initiated by the investigators. Aarhus University and The Research Foundation of the Department of Endocrinology and Internal Medicine and the Department of Clinical Epidemiology, Aarhus University Hospital, have granted financial support.

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Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark

    A.S. Sølling, T. Harsløf & B. Langdahl

  2. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark

    D.H. Christensen, B. Darvalics & R.W. Thomsen

Authors
  1. A.S. Sølling
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  2. D.H. Christensen
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  3. B. Darvalics
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  4. T. Harsløf
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  5. R.W. Thomsen
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  6. B. Langdahl
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Contributions

All authors contributed to the study.

Corresponding author

Correspondence to A.S. Sølling.

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Conflicts of interest

Anne Sophie Sølling has nothing to disclose.

Diana Hedevang Christensen has nothing to disclose.

Bianka Darvalics has nothing to disclose.

Torben Harsløf received lecture fees from Amgen, Astra Zeneca, and Eli Lilly.

Reimar Wernich Thomsen has nothing to disclose.

Bente Langdahl is an editor-in-chief of Bone Reports and an associate editor of the European Journal of Endocrinology and has received research funding to her institution from Amgen and Novo Nordisk. Bente Langdahl serves on advisory boards and speaker’s bureau for Amgen, Eli Lilly, Gedeon-Richter, Gilead, and UCB.

The Department of Clinical Epidemiology is involved in studies of osteoporosis with funding from various companies as research grants to (and administered by) Aarhus University.

Disclaimer

The Research Foundation was not involved in the conduct of the study, data collection, interpretation of the data, or the preparation of the manuscript.

Code availability

Please see supplementary Table 1 for International Classification of Diseases, Tenth Revision codes, procedure and NOMESCO surgery codes, and Anatomical Therapeutic Chemical classification system codes used in this study.

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Sølling, A., Christensen, D., Darvalics, B. et al. Fracture rates in patients discontinuing alendronate treatment in real life: a population-based cohort study. Osteoporos Int 32, 1103–1115 (2021). https://doi.org/10.1007/s00198-020-05745-x

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