Recent Stem-Cell-Based and Stem-Cell-Free Possibilities for the Therapeutic Management of the Osteonecrosis of the Jaw.

Osteonecrosis of the jaw (ONJ), including the maxilla and mandible, is considered a challenging therapeutic problem, mainly due to the lack of understanding of its pathogenesis. It is well known that ONJ is a severe side effect caused by certain medications used to treat bone metastasis and osteoporosis, such as bisphosphonates, which inhibit bone resorption. Other therapeutics with similar side effects are, for instance, receptor activators of nuclear factor kappa-B ligand (RANK-L) inhibitor (denosumab), tyrosine kinase inhibitors (sunitinib), and antiangiogenics (bevacizumab). The conservative or surgical treatment of these medication-related osteonecroses of the jaw (MRONJs) is generally effortful and still not entirely effective. Therefore, the research seeks alternative treatment options like tissue engineering and stem cell therapy, which predominantly represent mesenchymal stem cells (MSCs) and their derivatives, such as extracellular vesicles. Moreover, it was published that novel stem cell therapy could even prevent the onset of MRONJ. On the other hand, the administration of stem cells may also be accompanied by some other health risks, such as an increased chance of cancer metastasis occurrence in cancer patients. The current review paper summarizes the most recent progress in stem-cell-based and stem-cell-free treatment options for the ONJ. Similarly, we discuss this novel approach's future perspectives and possible obstacles.