Elevated levels of SAM can enhance this methylation, ultimately promoting osteoclast differentiation and bone resorption.30 Deleting DNMT3a in osteoclasts (OC) or using the inhibitor TF-3 in mice protects against bone loss after ovarian removal.31 Moreover, in multiple myeloma patients, alterations in bone resorption have been associated with elevated IRF8 methylation, induced by myeloma cells’ release of thymidine phosphorylase (TP), leading to decreased IRF8 expression and enhanced bone resorption.32 Here, IRF8 is linked to plasma cell myeloma.