HYPOTHESIS AND THEORY article
Front. Med.
Sec. Translational Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1584022
This article is part of the Research TopicInsights in Aging and the Immune System: 2025View all articles
THE UNEXPLORED RELATIONSHIP BETWEEN SPONTANEOUS OSTEOCLASTOGENESIS AND PLATELETS IN OSTEOPOROSIS
Provisionally accepted
Francesca Salamanna1
Alberto Corrado Di Martino2,3
Deyanira Contartese1*
Cesare Faldini2,3
Gianluca Giavaresi1
Milena Fini4- 1Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Emilia-Romagna, Italy
- 21st Orthopaedic and Traumatologic Department, Rizzoli Orthopedic Institute (IRCCS), Bologna, Emilia-Romagna, Italy
- 3Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Emilia-Romagna, Italy
- 4Scientific Direction, Rizzoli Orthopedic Institute (IRCCS), Bologna, Emilia-Romagna, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Spontaneous osteoclastogenesis, a phenomenon characterized by the unregulated differentiation and activation of osteoclasts in the absence of exogenous stimulatory factors, plays a central role in osteoporosis. While conventionally attributed to an imbalance between osteoclast and osteoblast activity, as well as to factors they release and/or produce, and to the involvement of T cells, emerging evidence suggests that platelets may contribute to this process beyond their established role in hemostasis. In this opinion, we propose that platelet activation and the subsequent release of cytokines, growth factors, and chemokines, including PDGF, IL1β, TGFβ, MIP-1α, TNFα, CXCL12 (SDF1), and CCL5 (RANTES), create a pro-inflammatory and osteoclastogenic microenvironment.These mediators may enhance RANKL production, recruit osteoclast precursors, and disrupt osteogenic signaling, indirectly fostering spontaneous osteoclastogenesis. Additionally, platelet interactions with endothelial cells, macrophages, and immune populations could further amplify inflammatory responses and sustain chronic bone resorption, contributing to the stimulation of spontaneous osteoclastogenesis. Although direct evidence linking platelets activation to spontaneous osteoclastogenesis is not yet available, existing literature supports the plausibility of this interplay.Exploring this underrecognized platelet-bone axis could provide new insights into osteoporosis pathophysiology and open avenues for novel diagnostic and therapeutic strategies. These hypotheses may be assessed in clinical practice to develop innovative approaches for the screening, diagnosis, monitoring and treatment of osteoporosis.
Keywords: Osteoporosis, spontaneous osteoclastogenesis, platelets, Cytokines, Chemokines, Endothelial Cells, immune cells
Received: 26 Feb 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Salamanna, Di Martino, Contartese, Faldini, Giavaresi and Fini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Deyanira Contartese, Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Emilia-Romagna, Italy
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.