Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology.
Angiogenesis Modulating Agents ; Cooperative Behavior ; Denosumab ; Dental Hygienists ; Dentists ; Diphosphonates ; Humans ; Immunomodulation ; Immunotherapy ; Jaw ; Oral and Maxillofacial Surgeons ; Oral Manifestations ; Osteonecrosis ; Pathology

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory.Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory.Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.