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Early changes in bone turnover and bone mineral density after discontinuation of long-term oral bisphosphonates: a post hoc analysis

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Abstract

Summary

This post hoc analysis of a randomized, double-blind study of postmenopausal women with osteoporosis found that there were early increases in bone turnover markers and decreases in bone mineral density after discontinuation of long-term alendronate. These findings might help guide treatment decisions, including monitoring after alendronate withdrawal.

Introduction

The short-term effects of discontinuing long-term bisphosphonates are poorly characterized. This post hoc analysis investigated 1–12-month changes in bone mineral density (BMD) and bone turnover markers (BTM) after alendronate (ALN) discontinuation.

Methods

Data were from a randomized, double-blind trial of MK-5442 (calcium-sensing receptor antagonist) following oral bisphosphonates, with placebo and continued ALN controls (ClinicalTrials.gov NCT00996801). Postmenopausal women with osteoporosis had received oral bisphosphonate (≥ 3–4 preceding years; ALN for the 12 months pre-screening), continuing on ALN 70 mg/week (n = 87) or placebo (n = 88).

Results

At 12 months, least-squares mean percent changes from baseline BMD (placebo vs. ALN) were lumbar spine (LS): – 0.36 vs. 1.29, total hip: – 1.44 vs. 0.46, and femoral neck (FN): – 1.26 vs. – 0.08 (all P < 0.05). BTM levels increased by 1–3 months, to 12 months, with placebo vs. ALN (P < 0.001). FN BMD decline was greater in the placebo subgroup with higher urinary N-terminal cross-linked telopeptides of type I collagen/creatinine [uNTx/Cr] (P < 0.01), and higher serum N-terminal pro-peptide of type 1 collagen [P1NP] levels (P < 0.05), at baseline. There was a trend toward greater FN BMD loss with higher BTM levels at 3 and/or 6 months. Younger age and higher LS BMD at baseline were associated with greater LS BMD loss at 12 months (P = 0.04 and < 0.01, respectively); higher baseline FN BMD predicted greater FN BMD loss (P = 0.04).

Conclusion

Early changes in BTM levels and BMD were observed after discontinuation of long-term ALN. Further characterization of factors associated with patients’ risk of bone loss upon bisphosphonate discontinuation is warranted.

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Acknowledgments

Medical writing assistance, under the direction of the authors, was provided by Annette Smith, PhD, of CMC AFFINITY, McCann Health Medical Communications, and Juliet George, PhD, on behalf of CMC AFFINITY, in accordance with Good Publication Practice (GPP3) guidelines. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Authors and Affiliations

  1. University of Alabama, Birmingham, AL, USA

    K. Saag

  2. Department of Medicine, Columbia University, New York, NY, USA

    F. Cosman

  3. Stellenbosch University and Mediclinic Panorama, Western Cape, South Africa

    T. De Villiers

  4. Aarhus University Hospital, Aarhus, Denmark

    B. Langdahl

  5. Merck & Co., Inc, Kenilworth, NJ, USA

    B.B. Scott, A.E. Denker, A. Pong & A.C. Santora

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  1. K. Saag
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Correspondence to K. Saag.

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Conflict of interest

Boyd B Scott, Annpey Pong, Andrew Denker, and Arthur C Santora are, or were at the time of study conduct, employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD), and may own stock and/or stock options in Merck & Co., Inc., Kenilworth, NJ, USA. Arthur C. Santora is Chief Medical Officer, Entera Bio Ltd. Kenneth Saag was a past consultant and investigator for MSD and has served as a consultant and investigator for Amgen, MSD, and Radius. Felicia Cosman was a consultant and advisor for MSD and is a consultant, advisor, and speaker for Amgen, Lilly, and Radius. Tobias De Villiers has participated in speaker panels for Abbott, Adcock Ingram, Aspen, MSD, and Pfizer Inc. Bente Langdahl was an advisor for MSD, is an advisor for Amgen, Lilly, and UCB, and has received research grants (for her institution) from Amgen and Novo Nordisk.

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Saag, K., Cosman, F., De Villiers, T. et al. Early changes in bone turnover and bone mineral density after discontinuation of long-term oral bisphosphonates: a post hoc analysis. Osteoporos Int 32, 1879–1888 (2021). https://doi.org/10.1007/s00198-020-05785-3

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