Introduction

The aim of the invention is to develop a remedy to cure Osteonecrosis of the Jaw (ONJ), a condition eventually determined as a frightening side effect by bisphosphonates; these drugs are successfully used, as osteoclasts inhibitors, in the therapy of diseases characterized by the loss of bone tissue such as Osteoporosis and Myeloma

Technical features

The invention has been carried out using osteoclasts obtained in culture through the stimulation of a monocyte – macrophage cell line with the proper differentiating agents, including Vitamin D3 (VD3). To mimic the situation of a patient under therapy with Bisphosphonates, such cells were also subjected to treatment with: Zoledronate (ZA), the most powerful among them, Magnesium Chloride (MgCl2), to evaluate its capacity to counteract ZA effect, both the compounds and, as a control, none of them. As expected, ZA inhibited osteoclast differentiation but MgCl2 abrogated its effect creating a sort of paradox effect that resulted in a powerful activation of the same process. On the other side, used autonomously, MgCl2 anyway induced a strong activation of osteoclast differentiation, even to a lesser extent, and amplified VD3 effect. It reaches TRL=3.

Possible Applications

• Oral prevention of ONJ with toothpaste, mouthwash or gel containing MgCl2;
• Surgical prevention of ONJ with powder, membrane, sponge, granulate of same content;
• Topic therapy of ONJ lesions with the same devices listed at the previous point.

Advantages

MgCl2 locally reactivates osteoclastic function:

• Inhibited by systemic bisphosphonate therapy;
• In the presence of therapies with Denosumab or similar;
• In the presence of systemic therapy with Vitamin D3.