Denosumab Discontinuation: the Abaloparatide plus Bisphosphonate Metronomic Sequential Approach

Denosumab Discontinuation: the Abaloparatide plus Bisphosphonate Metronomic Sequential Approach | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 2 September 2025 V1 Latest version Share on Denosumab Discontinuation: the Abaloparatide plus Bisphosphonate Metronomic Sequential Approach Authors : M 0009-0004-8362-9249 [email protected] , Alberto Vassallo , Fanny Valsecchi , and Filippo Maria Bolamperti Authors Info & Affiliations https://doi.org/10.22541/au.175683892.26048418/v1 301 views 196 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background . Discontinuing denosumab (Dmab) causes a rapid increase in bone resorption, loss of bone mineral density (BMD), and clusters of rebound-associated vertebral fractures (RAFV). Current approaches, such as intravenous (IV) zoledronate (Zol), oral bisphosphonates (BPs), teriparatide (TPTD), romosozumab (Romo), selective estrogen receptor modulators (SERMs), and menopausal hormone therapy (MHT), have failed to provide protection consistently. Methods . We conducted a brief narrative review of randomized controlled trials (RCTs), observational cohorts, and mechanistic studies, as well as expert position papers (2015-2025), that focused on post-Dmab strategies and mechanistic models of remodeling. Results . Evidence consistently shows that Zol often requires repeated infusions and fails to prevent BMD decline or RAFV, especially after long-term Dmab therapy. Oral BPs are weaker and have limited adherence, TPTD worsens rebound resorption, and Romo provides only modest benefits. SERMs and MHT are largely ineffective. Once RAFV occurs, clinical outcomes remain poor despite rescue therapy. S. Bolamperti et al. suggested that complete osteoclast suppression abolishes coupling signals essential for bone formation, while BPs cannot neutralize osteomorph-driven resorption. Hypothesis . We suggest that a metronomic BP regimen (low doses or extended intervals), combined (initially) with abaloparatide (Abalo) and guided by personalized monitoring of the C-terminal telopeptide of type I collagen (CTX), may limit osteoclast activity without stopping anabolic signaling, thus preventing fractures and maintaining bone-forming capacity. Conclusions : A biologically informed, modulatory approach is a promising hypothesis that warrants future clinical testing and could redefine the paradigm of post-Dmab osteoporosis management. Supplementary Material File (denosumab discontinuation - the abaloparatide plus bisphosphonate metronomic sequential approach.pdf) Download 491.95 KB Information & Authors Information Version history V1 Version 1 02 September 2025 Copyright This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License Keywords abaloparatide alendronate ctx denosumab ects fractures metronomic therapy rebound Authors Affiliations M 0009-0004-8362-9249 [email protected] Institute of Endocrinology and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele View all articles by this author Alberto Vassallo Institute of Endocrinology and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele View all articles by this author Fanny Valsecchi Institute of Endocrinology and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele View all articles by this author Filippo Maria Bolamperti Institute of Endocrinology and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele View all articles by this author Metrics & Citations Metrics Article Usage 301 views 196 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation M, Alberto Vassallo, Fanny Valsecchi, et al. Denosumab Discontinuation: the Abaloparatide plus Bisphosphonate Metronomic Sequential Approach. Authorea . 02 September 2025. DOI: https://doi.org/10.22541/au.175683892.26048418/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); Cited by Marco Bonifacio, Marco Ruggiero, Linda Lucchetti, Marco Giuseppe Musorrofiti, Giuseppe La Cava, Alessandro Chiappetta, Emanuele Fiorino, Alberto Lo Gullo, Alessandro Conforti, The Efficacy and Safety of Abaloparatide in Osteoporosis: A Systematic Review and Meta-Analysis, Journal of Clinical Medicine, 15 , 2, (673), (2026). https://doi.org/10.3390/jcm15020673 Crossref Loading... View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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