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SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation

Denosumab (DMAb) is a soluble inhibitor of RANKL and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with the reversal of the effects attained with treatment. Concerns have been raised regarding possible increased vertebral fragility following...

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Autores principales: Zanchetta, Maria Belen, Pelegrin, Carolina, Sarli, Marcelo, miechi, lara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552094/
http://dx.doi.org/10.1210/js.2019-SAT-532
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author Zanchetta, Maria Belen
Pelegrin, Carolina
Sarli, Marcelo
miechi, lara
author_facet Zanchetta, Maria Belen
Pelegrin, Carolina
Sarli, Marcelo
miechi, lara
author_sort Zanchetta, Maria Belen
collection PubMed
description Denosumab (DMAb) is a soluble inhibitor of RANKL and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with the reversal of the effects attained with treatment. Concerns have been raised regarding possible increased vertebral fragility following denosumab discontinuation due to a rebound in bone turnover to values above pretreatment levels and accompanying rapid bone loss. Bisphophonates administration has been recommended to avoid rapid bone loss but few studies have addressed this question.Aim: Compare BMD and bone turnover markers between patients who had received bisphosphonates after stopping DMab and those who had not.Material &Methods: Postmenopausal women who had received at least two consecutive doses and had discontinued DMab were invited to this prospective and observational study. They were divided into two groups according to whether they had received bisphosphonates or not (Treated Group vs Non-treated Group). Treatment´s decisions were made by each patient and their primary physician.All patients had a DXA scan done (LS and FN) (Lunar Prodigy Advance, software 13.6), spine RX and bone turnovers markers evaluated (C-telopeptide (CTx) (electrochemiluminescence ) and osteocalcin (electrochemiluminescence) baseline (+ 6 months after last DMab ) and annually (+18 months after DMab).Results: 33 postmenopausal women completed the first year of follow up: 23 from the Non-treated Group and 10 from the Treated one. After 18 months of the last DMab dose, in the first group we observed a significant reduction in LS BMD (- 6.4 ± 6.6 %; p < 0.01) and FN BMD (- 6 ± 5.4 %; p <0.01). In the Treated Group, LS BMD was 3.6 ± 4.5% lower than baseline (p=0.05) and FN 1 ± 3.7 % lower (P=0.29). Comparing both groups, there was no significant difference in LS BMD (p= 0.19) but a significant one in FN BMD (p =0.02).CTx values increased 1063 ± 738 % (P < 0.01) in the Non- treated Group and 373 ± 333.5 % in the Treated Group (P <0.01), with a significant difference between them (P< 0.01). Osteocalcin increased 264 ± 200 % (P <0.01) and 131 ± 102 % (p <0.01) respectively, with no significant differences between groups (P 0.06). No new vertebral fractures were found in any patient ´s spine RX.Conclusion: In this study,we showed that bisphosphonates decreased bone loss both in LS and FN after DMab discontinuation and prevented the rebound of bone remodeling markers.More studies are needed to confirm the role of bisphosphonates in the long term and the best strategy to give them. Meanwhile, it is important to enhance physicians’ awareness of the need to start bisphosphonates after discontinuing DMab.
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spelling pubmed-65520942019-06-13 SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation Zanchetta, Maria Belen Pelegrin, Carolina Sarli, Marcelo miechi, lara J Endocr Soc Bone and Mineral Metabolism Denosumab (DMAb) is a soluble inhibitor of RANKL and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with the reversal of the effects attained with treatment. Concerns have been raised regarding possible increased vertebral fragility following denosumab discontinuation due to a rebound in bone turnover to values above pretreatment levels and accompanying rapid bone loss. Bisphophonates administration has been recommended to avoid rapid bone loss but few studies have addressed this question.Aim: Compare BMD and bone turnover markers between patients who had received bisphosphonates after stopping DMab and those who had not.Material &Methods: Postmenopausal women who had received at least two consecutive doses and had discontinued DMab were invited to this prospective and observational study. They were divided into two groups according to whether they had received bisphosphonates or not (Treated Group vs Non-treated Group). Treatment´s decisions were made by each patient and their primary physician.All patients had a DXA scan done (LS and FN) (Lunar Prodigy Advance, software 13.6), spine RX and bone turnovers markers evaluated (C-telopeptide (CTx) (electrochemiluminescence ) and osteocalcin (electrochemiluminescence) baseline (+ 6 months after last DMab ) and annually (+18 months after DMab).Results: 33 postmenopausal women completed the first year of follow up: 23 from the Non-treated Group and 10 from the Treated one. After 18 months of the last DMab dose, in the first group we observed a significant reduction in LS BMD (- 6.4 ± 6.6 %; p < 0.01) and FN BMD (- 6 ± 5.4 %; p <0.01). In the Treated Group, LS BMD was 3.6 ± 4.5% lower than baseline (p=0.05) and FN 1 ± 3.7 % lower (P=0.29). Comparing both groups, there was no significant difference in LS BMD (p= 0.19) but a significant one in FN BMD (p =0.02).CTx values increased 1063 ± 738 % (P < 0.01) in the Non- treated Group and 373 ± 333.5 % in the Treated Group (P <0.01), with a significant difference between them (P< 0.01). Osteocalcin increased 264 ± 200 % (P <0.01) and 131 ± 102 % (p <0.01) respectively, with no significant differences between groups (P 0.06). No new vertebral fractures were found in any patient ´s spine RX.Conclusion: In this study,we showed that bisphosphonates decreased bone loss both in LS and FN after DMab discontinuation and prevented the rebound of bone remodeling markers.More studies are needed to confirm the role of bisphosphonates in the long term and the best strategy to give them. Meanwhile, it is important to enhance physicians’ awareness of the need to start bisphosphonates after discontinuing DMab. Endocrine Society 2019-04-30 /pmc/articles/PMC6552094/ http://dx.doi.org/10.1210/js.2019-SAT-532 Text en Copyright © 2019 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Bone and Mineral Metabolism
Zanchetta, Maria Belen
Pelegrin, Carolina
Sarli, Marcelo
miechi, lara
SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation
title SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation
title_full SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation
title_fullStr SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation
title_full_unstemmed SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation
title_short SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation
title_sort sat-532 bisphosphonates prevent bone loss associated with denosumab treatment discontinuation
topic Bone and Mineral Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552094/
http://dx.doi.org/10.1210/js.2019-SAT-532
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