Supra-Physiological Levels of Magnesium Counteract the Inhibitory Effect of Zoledronate on RANKL-Dependent Osteoclastogenesis

Bisphosphonates (BPs) are drugs used to cure metabolic diseases like osteoporosis and oncological conditions, such as multiple myeloma and bone metastases. The pharmacological activity of these compounds is mediated by their capacity to induce a systemic osteoclast depletion, finally resulting in re...

Full description

Saved in:
Bibliographic Details
Main Authors: Lorenzo Caselli, Lisa De Pasquale, Rossella Palumbo, Silvia Ricchiuto, Monica Montanari, Sebastiano Rontauroli, Alessandra Ottani, Ruggiero Norfo, Tommaso Zanocco-Marani, Alexis Grande
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/14/5/533
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bisphosphonates (BPs) are drugs used to cure metabolic diseases like osteoporosis and oncological conditions, such as multiple myeloma and bone metastases. The pharmacological activity of these compounds is mediated by their capacity to induce a systemic osteoclast depletion, finally resulting in reduced bone resorption. In spite of their efficacy, the clinical application of BPs is sometimes associated with a frightening side effect known as osteonecrosis of the jaw (ONJ). In principle, a therapeutic approach able to elicit the local re-activation of osteoclast production could counteract the onset of ONJ and promote the healing of its lesions. Using a vitamin D3-dependent model of osteoclast differentiation, it has been previously demonstrated that when used at supra-physiological concentrations, magnesium strongly favors the process under consideration, and its effect is furtherly enhanced by the presence of a BP called zoledronate. Here, we show that similar results can be obtained in a RANKL-dependent model of osteoclast differentiation, suggesting that a topical therapy based on magnesium may be also suitable for ONJ determined by denosumab in light of the ability of this monoclonal antibody to target RANKL.
ISSN:2079-7737