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Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases

While de-escalation of bisphosphonates from 4 to 12-weekly dosing has been shown to be clinically non-inferior to standard dosing, there is evidence the de-escalation is associated with increased bone turnover biomarkers. Here we evaluated the effect of de-escalated dosing on a panel of biomarkers a...

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Autores principales: Addison, Christina L, Pond, Gregory R, Zhao, Huijun, Mazzarello, Sasha, Vandermeer, Lisa, Goldstein, Robyn, Amir, Eitan, Clemons, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194305/
https://www.ncbi.nlm.nih.gov/pubmed/25332877
http://dx.doi.org/10.1186/2193-1801-3-577
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author Addison, Christina L
Pond, Gregory R
Zhao, Huijun
Mazzarello, Sasha
Vandermeer, Lisa
Goldstein, Robyn
Amir, Eitan
Clemons, Mark
author_facet Addison, Christina L
Pond, Gregory R
Zhao, Huijun
Mazzarello, Sasha
Vandermeer, Lisa
Goldstein, Robyn
Amir, Eitan
Clemons, Mark
author_sort Addison, Christina L
collection PubMed
description While de-escalation of bisphosphonates from 4 to 12-weekly dosing has been shown to be clinically non-inferior to standard dosing, there is evidence the de-escalation is associated with increased bone turnover biomarkers. Here we evaluated the effect of de-escalated dosing on a panel of biomarkers and determined their association with incidence of skeletal related events (SREs) in breast cancer patients with ‘low risk’ bone metastases. As part of a pilot randomized trial, women with baseline C-telopeptide levels <600 ng/L after >3 months of 3–4 weekly pamidronate were randomized to continue pamidronate every 4 weeks or de-escalation to 12-weekly treatment. Serum was analysed for bone biomarkers (C-telopeptide, N-telopeptide, bone-specific alkaline phosphatase, transforming growth factor-β, procollagen type 1 N-propeptide, activinA and bone sialoprotein) using ELISA. The associations between changes in biomarkers, pain scores and SREs were assessed by univariable logistic regression. Numerical increases in all biomarkers were observed between baseline and 12 weeks but were of higher magnitude in the de-escalated arm. Pain scores in the de-escalated treatment arm showed a greater magnitude of pain reduction from baseline to 12 weeks. Neither baseline levels nor changes in biomarkers from baseline to 12 weeks on treatment were associated with on study SREs. Baseline pain as measured by the FACT-BP was associated with increased risk of SRE. In conclusion, biomarkers of bone activity do not appear to predict for SREs in ‘low risk’ cohorts. However, baseline bone pain appears to be associated with SRE occurrence, a finding which warrants evaluation in larger cohorts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-3-577) contains supplementary material, which is available to authorized users.
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spelling pubmed-41943052014-10-20 Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases Addison, Christina L Pond, Gregory R Zhao, Huijun Mazzarello, Sasha Vandermeer, Lisa Goldstein, Robyn Amir, Eitan Clemons, Mark Springerplus Research While de-escalation of bisphosphonates from 4 to 12-weekly dosing has been shown to be clinically non-inferior to standard dosing, there is evidence the de-escalation is associated with increased bone turnover biomarkers. Here we evaluated the effect of de-escalated dosing on a panel of biomarkers and determined their association with incidence of skeletal related events (SREs) in breast cancer patients with ‘low risk’ bone metastases. As part of a pilot randomized trial, women with baseline C-telopeptide levels <600 ng/L after >3 months of 3–4 weekly pamidronate were randomized to continue pamidronate every 4 weeks or de-escalation to 12-weekly treatment. Serum was analysed for bone biomarkers (C-telopeptide, N-telopeptide, bone-specific alkaline phosphatase, transforming growth factor-β, procollagen type 1 N-propeptide, activinA and bone sialoprotein) using ELISA. The associations between changes in biomarkers, pain scores and SREs were assessed by univariable logistic regression. Numerical increases in all biomarkers were observed between baseline and 12 weeks but were of higher magnitude in the de-escalated arm. Pain scores in the de-escalated treatment arm showed a greater magnitude of pain reduction from baseline to 12 weeks. Neither baseline levels nor changes in biomarkers from baseline to 12 weeks on treatment were associated with on study SREs. Baseline pain as measured by the FACT-BP was associated with increased risk of SRE. In conclusion, biomarkers of bone activity do not appear to predict for SREs in ‘low risk’ cohorts. However, baseline bone pain appears to be associated with SRE occurrence, a finding which warrants evaluation in larger cohorts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-3-577) contains supplementary material, which is available to authorized users. Springer International Publishing 2014-10-01 /pmc/articles/PMC4194305/ /pubmed/25332877 http://dx.doi.org/10.1186/2193-1801-3-577 Text en © Addison et al.; licensee Springer. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research
Addison, Christina L
Pond, Gregory R
Zhao, Huijun
Mazzarello, Sasha
Vandermeer, Lisa
Goldstein, Robyn
Amir, Eitan
Clemons, Mark
Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases
title Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases
title_full Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases
title_fullStr Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases
title_full_unstemmed Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases
title_short Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases
title_sort effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194305/
https://www.ncbi.nlm.nih.gov/pubmed/25332877
http://dx.doi.org/10.1186/2193-1801-3-577
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