In Vitro Cytotoxicity of Antiresorptive and Antiangiogenic Compounds on Oral Tissues Contributing to MRONJ: Systematic Review

• Published in: Biomolecules (Basel, Switzerland) Vol. 13; no. 6; p. 973
• Main Authors: Guirguis, Robert H, Tan, Leonard P, Hicks, Rebecca M, Hasan, Aniqa, Duong, Tina D, Hu, Xia, Hng, Jordan Y S, Hadi, Mohammad H, Owuama, Henry C, Matthyssen, Tamara, McCullough, Michael, Canfora, Federica, Paolini, Rita, Celentano, Antonio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.06.2023; MDPI
• Subjects: Adverse and side effects; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Antiangiogenic agents; antiangiogenics; antiresorptives; Bevacizumab; Bias; Bisphosphonate-Associated Osteonecrosis of the Jaw - drug therapy; Bisphosphonate-Associated Osteonecrosis of the Jaw - etiology; Bisphosphonates; Bone Density Conservation Agents - adverse effects; Bones; Causes of; Cell migration; Cell proliferation; Clodronic acid; Cytotoxicity; Denosumab - adverse effects; Development and progression; Diphosphonates - pharmacology; Diphosphonates - therapeutic use; Drug dosages; Drugs; Fibroblasts; Humans; Internal validity; Jaw; Jaw diseases; Keratinocytes; MRONJ; Necrosis; oral tissues; Osteonecrosis; Statistical analysis; Systematic Review; Vascular endothelial growth factor; Zoledronic Acid; Australia; antiangiogenics; bisphosphonates; oral tissues; MRONJ; antiresorptives
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom13060973

Invasive dental treatment in patients exposed to antiresorptive and antiangiogenic drugs can cause medication-related osteonecrosis of the jaw (MRONJ). Currently, the exact pathogenesis of this disease is unclear. In March 2022, Medline (Ovid), Embase (Ovid), Scopus, and Web of Science were screened to identify eligible in vitro studies investigating the effects of antiresorptive and antiangiogenic compounds on orally derived cells. Fifty-nine articles met the inclusion criteria. Bisphosphonates were used in 57 studies, denosumab in two, and sunitinib and bevacizumab in one. Zoledronate was the most commonly used nitrogen-containing bisphosphonate. The only non-nitrogen-containing bisphosphonate studied was clodronate. The most frequently tested tissues were gingival fibroblasts, oral keratinocytes, and alveolar osteoblasts. These drugs caused a decrease in cell proliferation, viability, and migration. Antiresorptive and antiangiogenic drugs displayed cytotoxic effects in a dose and time-dependent manner. Additional research is required to further elucidate the pathways of MRONJ.