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Cited by 119Bone health and osteoporosis researchBone health and treatmentsMenopause: Health Impacts and Treatments

Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study

Zanchetta, M. B., Boailchuk, J., Massari, F., Silveira, F., Bogado, C., Zanchetta, J. R.·2018·Osteoporosis International
DOI 10.1007/s00198-017-4242-6
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Abstract

We evaluate 38 elderly women who had received long-term denosumab treatment after stopping the drug. Taking into account the gain during treatment and the loss after stopping treatment, they lost 35.5% of the total gain in the spine, 44.6% of the total gain in the femoral neck, and 103.3% in the total hip.Introduction Denosumab (DMAb) is a soluble inhibitor of the receptor activator of nuclear factor-kappaB ligand (RANKL) and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with reversal of the effects attained with treatment.Purpose The aim of this study is to assess changes in BMD after a year of discontinuation of DMAb in a group of postmenopausal women treated with DMAb for 7 or 10 years. Secondly, is to evaluate the occurrence of fragility fractures.Methods Women who had participated in the FREEDOM study and its extension were invited to participate in this follow-up study. BMD at LS and hip and spine X-rays were obtained. Results were compared to the last value obtained while in treatment to assess changes after discontinuation.Results Thirty-eight women, mean age: 81 ± 3.4 years completed study procedures; none had received bisphosphonates after stopping DMAb. Mean gap time between DMAb last dose and the follow-up visit was 17 months (range 16-20 months). Bone mineral density (BMD) decreased significantly in all regions: - 8.1% in LS, - 6% in FN, and - 8.4% in TH. Five (5/38, 13.15%) patients had a fragility fracture, one suffered a wrist fracture, and four experienced vertebral fractures. Three patients suffered one vertebral fracture and one of them had two vertebral fractures. Laboratory results showed the following mean values: CTX = 996 ± 307 pg/ml (normal values 550 ± 226 pg/ml); osteocalcin = 55.2 ± 18.6 ng/ml (normal value 42 ng/ml); and 25 OH vitamin D = 23.7 ± 6.9 ng/ml.Conclusion Our results describe the rapid bone loss occurring after cessation of denosumab treatment. Further studies are needed to assess if patients have a higher risk of fracture after stopping DMAb and if so, which patients have the highest risk, and assess the role of transitioning to bisphosphonates in the long term.

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  • Reconstitution of RANKL signaling, as occurs upon DMAB discontinuation, can activate massive bone resorption over a very short time scale, leading to rebound fractures.

    “Since RANKL inhibition by DMAB results in osteomorph accumulation,257 the reconstitution of RANKL signaling, as occurs upon DMAB discontinuation, can activate massive bone resorption over a very short time scale, leading to rebound fractures.260”

    From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [260]

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Authors
Zanchetta, M. B., Boailchuk, J., Massari, F., Silveira, F., Bogado, C., & Zanchetta, J. R.
Affiliations
  • Universidad del Salvador (AR)
  • Instituto de Diagnóstico e Investigaciones Metabólicas (AR)
Corresponding author
Zanchetta, M. B.
ORCID
Venue
Osteoporosis International
Publisher
Springer Science and Business Media LLC
Published
2017-10-03
Volume
29
Issue
1
Pages
41-47
ISSN
  • 0937-941X (ISSN-L)
  • 1433-2965
DOI
10.1007/s00198-017-4242-6
OpenAlex
W2764233026
Cited by
119
References
20
Citations by year
2026: 9 · 2025: 12 · 2024: 14 · 2023: 16 · 2022: 10 · 2021: 19 · 2020: 11 · 2019: 19 · 2018: 9
FWCI
11.78
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • Osteoporosis International (publishedVersion)
  • PubMed (publishedVersion)
Funders
Amgen
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Oncology › Bone health and treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords
denosumab, RANKL inhibitor, treatment discontinuation, bone loss, bone mineral density, postmenopausal women, older women, fragility fractures, vertebral fractures, osteocalcin, CTX, 25-hydroxyvitamin D, osteoporosis, bisphosphonates
MeSH terms
Deprescriptions, Denosumab, Aged, Aged, 80 and over, Drug Administration Schedule, Female, Femur Neck, Follow-Up Studies, Hip Joint, Humans, Lumbar Vertebrae, Absorptiometry, Photon, Bone Density, Osteoporosis, Postmenopausal, Withholding Treatment, Bone Density Conservation Agents, Osteoporotic Fractures

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