them more potent than nonNBPs.6 Consequently, NBPs also have a higher risk of inducing MRONJ.6 In 2009, the United States Food and Drug Administration approved the monoclonal antibody denosumab for the treatment of osteoporosis, bone metastasis, and giant cell tumors.7 Deno- sumab inhibits osteoclast recruitment and action.8,9 In 2019, another monoclonal antibody, romosozumab, was approved for osteoporosis treatment, as it decreases vertebral fracture risk. This drug enhances bone formation and reduces bone resorption. Cases of MRONJ were reported in the romosozumab registration trial, though the real-world incidence is not known.10 Angiogenesis is required for tumor development and cancer progression.11 Antiangiogenic drugs, used in cancer treatment, block the angiogenesis signaling cascade and prevent new blood vessel formation.11 Osteonecrosis is classically associated with decreased blood flow to the affected bone, and the function of these medications likely contributes to MRONJ. These drugs are broadly divided into tyrosine kinase inhibitors (TKIs) and monoclonal antibodies.11,12 TKIs, such as sunitinib and sorafenib, inhibit phosphorylation of receptors involved with vascu- lar endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor.11 Mon- oclonal antibodies, including bevacizumab, target VEGFR or VEGFR2.11 More MRONJ cases are associated with the use of antiresorptive drugs, with a smaller number resulting from antiangio- genic medications.13,14 However, there is a current literature gap on antiangiogenic medications in MRONJ development. MRONJ incidences vary depending on the indication for treatment. When antiresorptive or antiangiogenic medications are used for cancer therapy, drug doses tend to be higher. When these medications are used to treat nonmalignant diseases, the doses are lower and reflect a decreased MRONJ risk. Osteoporosis is the most common nonmalignant condition that poses a risk for MRONJ. However, other at-risk nonmalignant diseases are osteogenesis imperfecta, chronic kidney dis- ease, and Paget disease. The cumulative dose is the duration and frequency of drug administra- tion, and a higher cumulative dose corresponds to a higher MRONJ risk, which is why it is necessary to know how long a patient has been on drug therapy.15 Additionally, intravenous administration of antiresorptive medications shows increased MRONJ prevalence and severity compared to oral intake.9 Although incidences of patients spontaneously developing MRONJ after taking antiresorptive or antiangiogenic medications have been reported, MRONJ is rare; most cases develop after a dental event.16 Extractions are the number one dental risk factor for MRONJ and, for this reason, clinicians need to be aware of all possible oral issues that may necessitate tooth removal. Interestingly, the area that a tooth is extracted from is significant — posterior tooth extractions are six times more likely to cause MRONJ compared to anterior extractions.17 Additionally, MRONJ is more prevalent in the mandible (75%), than in the maxilla (25%); however 4.5% of patients expe- rience MRONJ in both jaws.4 Periodontal diseases are another significant risk factor in the development of MRONJ, and the reason that more than 60% of teeth need extraction in patients ages 45 and older.18 Periodontal diseases are characterized by inflammation and result in catabolism of the supporting jawbone.18 Other dental comorbidities associated with MRONJ include denture trauma, implants, infection/abscess, and general poor oral health.19,20 Demographic factors show that women older than age 65 are at the highest risk, likely due to breast cancer and osteoporosis diagnoses.21 The most recent AAOMS position paper states that corticosteroid use in conjunction with antiresorptive drugs increases MRONJ risk.4 One recent cohort study showed that patients with multiple myeloma, followed by breast and prostate can- cers, are at highest risk.19,20 Other studies show tobacco use and cardiovascular disease as medical comorbidities that increase MRONJ risk, although many systemic chronic conditions that influence MRONJ development are still being debated in the literature.4,19 NITA SINGH, DDS, is a dual- degree student at the University of Michigan School of Dentistry in Ann Arbor. She is currently a doctoral candidate in the school’s Surface lab, where she is investigating nitrogen-containing bisphosphonates in the development of medication-related osteonecrosis of the jaw and other diseases. A resident in the pediatric dental program, Singh can be reached at [email protected]. LAUREN SURFACE, PhD, is an assistant professor in the Department of Biologic and Materials Sciences at the University of Michigan School of Dentistry, where her lab investigates various aspects of bone health in aging and disease. The authors have no commercial conflicts of interest to disclose. dimensionsofdentalhygiene.com January/February 2024 • Dimensions OF DENTAL HYGIENE 39 DIMENSIONS CE
