Clinical experience with denosumab discontinuation

Natasha Laursen; Anne Sophie Sølling; Torben Harsløf; Bente Langdahl

doi:10.1007/s00198-024-07351-7

Clinical experience with denosumab discontinuation

Natasha Laursen^*, Anne Sophie Sølling, Torben Harsløf, Bente Langdahl

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

Abstract

Summary: In patients receiving long-term treatment with denosumab, denosumab discontinuation via sequential treatment with zoledronate, resulted in a minor decrease in bone mass density (BMD) of 0–2.5% within the first year and stabile BMD in the second year, thus showing that repeated treatments with zoledronate limit the loss of BMD, when discontinuing denosumab. Purpose: Discontinuing denosumab (DMAb) rapidly decreases bone mineral density (BMD) and increases the risk of multiple vertebral fractures. We wanted to examine if the recommendation stated in the ECTS position paper on DMAb discontinuation can prevent the bone loss in a clinical setting. Methods: We conducted a retrospective cohort study based on medical records of patients referred for DMAb discontinuation. We administered zoledronate (ZOL) 6 months after the last DMAb injection and 3, 6, 12, and 24 months thereafter if p-C-terminal collagen crosslinks (CTX) increased above 0.5 μg/l or BMD decreased (≥ 5% at the hip, ≥ 3% at the spine) at months 12 and 24. Results: We included 66 women and men discontinuing DMAb after a mean treatment duration of 6.7 ± 2.7 (mean ± SD) years. BMD decreased 12 months after the initial ZOL treatment by 2.5 ± 4.2% and 1.9 ± 2.5% at the LS and TH, respectively (n = 44) (p ≤ 0.001 for all). There was no significant change in FNBMD (0.0 ± 5.1) (p > 0.05). No significant change in BMD was seen from month 12 to month 24 at any site (p > 0.05 for all). Thirty percent and twenty-two percent of patients experienced flu-like symptoms after the first and second ZOL infusion. No fractures occurred during the study period. Conclusion: Adhering to the recommendation in the ECTS position statement, a mean of 3 infusions of ZOL limited the bone loss 12 and 24 months after DMAb discontinuation, thereby preserving most of the BMD gained during DMAb treatment. The frequent occurrence of flu-like symptoms after ZOL proves to be a challenge, showing that routine prophylaxis against acute phase responses should be considered in patients treated with ZOL after discontinuing DMAb.

Original language	English
Article number	e10731
Journal	Osteoporosis International
Volume	36
Issue	3
Pages (from-to)	435-446
Number of pages	12
ISSN	0937-941X
DOIs	https://doi.org/10.1007/s00198-024-07351-7
Publication status	Published - Mar 2025

Keywords

Bisphosphonates
Denosumab
Discontinuation
Osteoporosis
Zoledronate

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10.1007/s00198-024-07351-7

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@article{daec7f8dc79542a09a82eef9c88d0f9b,

title = "Clinical experience with denosumab discontinuation",

abstract = "Summary: In patients receiving long-term treatment with denosumab, denosumab discontinuation via sequential treatment with zoledronate, resulted in a minor decrease in bone mass density (BMD) of 0–2.5% within the first year and stabile BMD in the second year, thus showing that repeated treatments with zoledronate limit the loss of BMD, when discontinuing denosumab. Purpose: Discontinuing denosumab (DMAb) rapidly decreases bone mineral density (BMD) and increases the risk of multiple vertebral fractures. We wanted to examine if the recommendation stated in the ECTS position paper on DMAb discontinuation can prevent the bone loss in a clinical setting. Methods: We conducted a retrospective cohort study based on medical records of patients referred for DMAb discontinuation. We administered zoledronate (ZOL) 6 months after the last DMAb injection and 3, 6, 12, and 24 months thereafter if p-C-terminal collagen crosslinks (CTX) increased above 0.5 μg/l or BMD decreased (≥ 5% at the hip, ≥ 3% at the spine) at months 12 and 24. Results: We included 66 women and men discontinuing DMAb after a mean treatment duration of 6.7 ± 2.7 (mean ± SD) years. BMD decreased 12 months after the initial ZOL treatment by 2.5 ± 4.2% and 1.9 ± 2.5% at the LS and TH, respectively (n = 44) (p ≤ 0.001 for all). There was no significant change in FNBMD (0.0 ± 5.1) (p > 0.05). No significant change in BMD was seen from month 12 to month 24 at any site (p > 0.05 for all). Thirty percent and twenty-two percent of patients experienced flu-like symptoms after the first and second ZOL infusion. No fractures occurred during the study period. Conclusion: Adhering to the recommendation in the ECTS position statement, a mean of 3 infusions of ZOL limited the bone loss 12 and 24 months after DMAb discontinuation, thereby preserving most of the BMD gained during DMAb treatment. The frequent occurrence of flu-like symptoms after ZOL proves to be a challenge, showing that routine prophylaxis against acute phase responses should be considered in patients treated with ZOL after discontinuing DMAb.",

keywords = "Bisphosphonates, Denosumab, Discontinuation, Osteoporosis, Zoledronate",

author = "Natasha Laursen and S{\o}lling, {Anne Sophie} and Torben Harsl{\o}f and Bente Langdahl",

note = "Publisher Copyright: {\textcopyright} International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation 2025.",

year = "2025",

month = mar,

doi = "10.1007/s00198-024-07351-7",

language = "English",

volume = "36",

pages = "435--446",

journal = "Osteoporosis International",

issn = "0937-941X",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "3",

}

TY - JOUR

T1 - Clinical experience with denosumab discontinuation

AU - Laursen, Natasha

AU - Sølling, Anne Sophie

AU - Harsløf, Torben

AU - Langdahl, Bente

N1 - Publisher Copyright: © International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation 2025.

PY - 2025/3

Y1 - 2025/3

N2 - Summary: In patients receiving long-term treatment with denosumab, denosumab discontinuation via sequential treatment with zoledronate, resulted in a minor decrease in bone mass density (BMD) of 0–2.5% within the first year and stabile BMD in the second year, thus showing that repeated treatments with zoledronate limit the loss of BMD, when discontinuing denosumab. Purpose: Discontinuing denosumab (DMAb) rapidly decreases bone mineral density (BMD) and increases the risk of multiple vertebral fractures. We wanted to examine if the recommendation stated in the ECTS position paper on DMAb discontinuation can prevent the bone loss in a clinical setting. Methods: We conducted a retrospective cohort study based on medical records of patients referred for DMAb discontinuation. We administered zoledronate (ZOL) 6 months after the last DMAb injection and 3, 6, 12, and 24 months thereafter if p-C-terminal collagen crosslinks (CTX) increased above 0.5 μg/l or BMD decreased (≥ 5% at the hip, ≥ 3% at the spine) at months 12 and 24. Results: We included 66 women and men discontinuing DMAb after a mean treatment duration of 6.7 ± 2.7 (mean ± SD) years. BMD decreased 12 months after the initial ZOL treatment by 2.5 ± 4.2% and 1.9 ± 2.5% at the LS and TH, respectively (n = 44) (p ≤ 0.001 for all). There was no significant change in FNBMD (0.0 ± 5.1) (p > 0.05). No significant change in BMD was seen from month 12 to month 24 at any site (p > 0.05 for all). Thirty percent and twenty-two percent of patients experienced flu-like symptoms after the first and second ZOL infusion. No fractures occurred during the study period. Conclusion: Adhering to the recommendation in the ECTS position statement, a mean of 3 infusions of ZOL limited the bone loss 12 and 24 months after DMAb discontinuation, thereby preserving most of the BMD gained during DMAb treatment. The frequent occurrence of flu-like symptoms after ZOL proves to be a challenge, showing that routine prophylaxis against acute phase responses should be considered in patients treated with ZOL after discontinuing DMAb.

AB - Summary: In patients receiving long-term treatment with denosumab, denosumab discontinuation via sequential treatment with zoledronate, resulted in a minor decrease in bone mass density (BMD) of 0–2.5% within the first year and stabile BMD in the second year, thus showing that repeated treatments with zoledronate limit the loss of BMD, when discontinuing denosumab. Purpose: Discontinuing denosumab (DMAb) rapidly decreases bone mineral density (BMD) and increases the risk of multiple vertebral fractures. We wanted to examine if the recommendation stated in the ECTS position paper on DMAb discontinuation can prevent the bone loss in a clinical setting. Methods: We conducted a retrospective cohort study based on medical records of patients referred for DMAb discontinuation. We administered zoledronate (ZOL) 6 months after the last DMAb injection and 3, 6, 12, and 24 months thereafter if p-C-terminal collagen crosslinks (CTX) increased above 0.5 μg/l or BMD decreased (≥ 5% at the hip, ≥ 3% at the spine) at months 12 and 24. Results: We included 66 women and men discontinuing DMAb after a mean treatment duration of 6.7 ± 2.7 (mean ± SD) years. BMD decreased 12 months after the initial ZOL treatment by 2.5 ± 4.2% and 1.9 ± 2.5% at the LS and TH, respectively (n = 44) (p ≤ 0.001 for all). There was no significant change in FNBMD (0.0 ± 5.1) (p > 0.05). No significant change in BMD was seen from month 12 to month 24 at any site (p > 0.05 for all). Thirty percent and twenty-two percent of patients experienced flu-like symptoms after the first and second ZOL infusion. No fractures occurred during the study period. Conclusion: Adhering to the recommendation in the ECTS position statement, a mean of 3 infusions of ZOL limited the bone loss 12 and 24 months after DMAb discontinuation, thereby preserving most of the BMD gained during DMAb treatment. The frequent occurrence of flu-like symptoms after ZOL proves to be a challenge, showing that routine prophylaxis against acute phase responses should be considered in patients treated with ZOL after discontinuing DMAb.

KW - Bisphosphonates

KW - Denosumab

KW - Discontinuation

KW - Osteoporosis

KW - Zoledronate

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U2 - 10.1007/s00198-024-07351-7

DO - 10.1007/s00198-024-07351-7

M3 - Journal article

C2 - 39777495

AN - SCOPUS:85217269238

SN - 0937-941X

VL - 36

SP - 435

EP - 446

JO - Osteoporosis International

JF - Osteoporosis International

IS - 3

M1 - e10731

ER -

Clinical experience with denosumab discontinuation

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