Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronic Acid

Silvia Ricchiuto
ORCID logo ,
Rossella Palumbo
,
Francesca Lami
,
Francesca Gavioli
,
Lorenzo Caselli
ORCID logo ,
Monica Montanari
,
Vincenzo Zappavigna
,
Alexandre Anesi
ORCID logo ,
Tommaso Zanocco-Marani
,
Alexis Grande
*
Version 1 : Received: 16 August 2023 / Approved: 16 August 2023 / Online: 17 August 2023 (09:26:11 CEST)

A peer-reviewed article of this Preprint also exists.

Ricchiuto, S.; Palumbo, R.; Lami, F.; Gavioli, F.; Caselli, L.; Montanari, M.; Zappavigna, V.; Anesi, A.; Zanocco-Marani, T.; Grande, A. The Capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronate. Biology 2023, 12, 1297. Ricchiuto, S.; Palumbo, R.; Lami, F.; Gavioli, F.; Caselli, L.; Montanari, M.; Zappavigna, V.; Anesi, A.; Zanocco-Marani, T.; Grande, A. The Capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronate. Biology 2023, 12, 1297.

Abstract

Bisphosphonates (BPs) are successfully used to cure a number of bone diseases characterized by metabolic osteopenia, such as Osteoporosis, or neoplastic osteolysis, such as Multiple Myeloma and Bone Metastases. These drugs exert their therapeutic effect inducing a systemic osteoclast depletion that, in turn, is responsible for a reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as Osteonecrosis of the Jaw (ONJ). It is generally believed that the inability of osteoclasts to get rid of inflamed / necrotic bone tissue represents the main physio-pathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. We have previously demonstrated that Magnesium (Mg) is a powerful inducer of osteoclast differentiation. Using a model of Vitamin D3 – dependent osteoclastogenesis, based on the U937 cell line, here we show that, surprisingly, this property of Mg is greatly enhanced by the presence of Zoledronic Acid (ZA), chosen for our study because it is the most effective among BPs. This finding allow us to hypothesize that Mg might play an important role in the topical therapy of ONJ.

Keywords

bisphosphonates; zoledronate; ONJ; osteoclasts; magnesium; differentiation

Subject

Medicine and Pharmacology, Dentistry and Oral Surgery

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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