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Treatment with zoledronic acid subsequent to odanacatib prevents bone loss in postmenopausal women with osteoporosis

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Abstract

Summary

Treatment with zoledronic acid 5 mg maintained bone turnover markers in the premenopausal range, increased lumbar spine bone mineral density, and maintained hip bone mineral density in women previously treated with odanacatib 50 mg weekly.

Introduction

The development of odanacatib (ODN), a cathepsin K inhibitor, for treatment of osteoporosis was discontinued due to an increased risk of cardiovascular events. As the treatment is considered reversible, participants from the LOFT trial in Aarhus, Denmark, were offered treatment with zoledronic acid (ZOL).

Methods

Sixty-seven postmenopausal women were treated with ZOL 5 mg and followed for 12 months. Of these, 39 had received ODN for 7 years and 28 had received placebo for 5 years and ODN for 2 years. Bone turnover markers (BTM) were measured 3, 6, and 12 months after ZOL, and DXA of spine and hip were performed at time of ZOL treatment and after 12 months.

Results

Within the entire study population, BMD at the lumbar spine increased by 2.8 ± 0.9% (mean ± SEM) (p < 0.01) from baseline to month 12. There was no significant change in BMD at the total hip (p = 0.17) or femoral neck (p = 0.39). There was no difference in the changes in BMD from baseline to 12 months between the two groups at any site (p ≥ 0.20 for all). CTX increased by 107 ± 9% (p < 0.001), PINP by 102 ± 16% (p < 0.001), osteocalcin by 32 ± 6% (p = 0.001) and BSAP by 79 ± 37% (p = 0.001) between 3 and 12 months after ZOL. At month 12, BTM were still within the premenopausal reference range. S-25-hydroxyvitamin D increased (p = 0.059), while PTH (p = 0.007) and eGFR (p = 0.014) decreased during the year following ZOL administration.

Conclusion

Treatment with ZOL 5 mg maintained BTMs in the premenopausal range and prevented bone loss in women previously treated with ODN.

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Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200, Aarhus N, Denmark

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

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  1. A.S. Koldkjær Sølling
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  2. T. Harsløf
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  3. B. Langdahl
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Correspondence to A.S. Koldkjær Sølling.

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Conflict of interest

Torben Harsløf received lecture fees from Amgen, Astra Zeneca, and Eli Lilly. Bente Langdahl is a consultant for MSD, Amgen, Eli Lilly, and UCB and has received lecture fees from MSD, Eli Lilly, and Amgen. Anne Sophie Koldkjær Sølling has nothing to declare.

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Koldkjær Sølling, A., Harsløf, T. & Langdahl, B. Treatment with zoledronic acid subsequent to odanacatib prevents bone loss in postmenopausal women with osteoporosis. Osteoporos Int 30, 995–1002 (2019). https://doi.org/10.1007/s00198-018-04833-3

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