Medication-Related Osteonecrosis of the Jaws (MRONJ): Etiological Update

Abstract

Osteonecrosis of the jaws (ONJ) is an uncommon but severe bone disease, can be related to various medicaments (MRONJ) including
bisphosphonates (BRONJ), antiangiogenic and antiresorptive medicaments such as Denosumab (DRONJ), human monoclonal
antibody to the receptor activator of nuclear factor-kB ligand. The rise in number in the latest years can be explained with many
patients treated with all these drugs, assumed for osteometabolic (i.e osteoporosis, osteogenesis imperfecta) or neoplastic diseases
(multiple myeloma, metastatic breast, prostate and renal cancer). The onset mechanism of MRONJ is not entirely understood,
probably different mechanisms are involved, such as inhibition of the osteoclasts differentiation and function, decrease of the
angiogenesis and inflammation/infection of the jaw bones. Some pathogenetic mechanisms are different according to the drugs, for
example the cases of the RANK-ligand inhibitor related ONJ may occur without considering the period of medication intake; also the
risk of ONJ manifestation after bisphosphonates (BF) is not significantly diminished after interrupting the drug therapy, because BF
bind to the bone matrix for many years. Drugs currently implicated in osteonecrosis pathology are various, therefore the term ONJ
was currently replaced by MRONJ; it is necessary that the anamnestic phase and management of the patients to be more detailed and
correct, not only to prevent osteonecrosis but also to plan all necessary treatments before start of the drug therapy.