Identified Medications Causing Medication-Related Osteonecrosis of the Jaw: A Literature Review

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse event that occurs in patients treated with certain medications, leading to a major side effect that can result in substantial morbidity. MRONJ is known to be associated with antiresorptive (AR) and antiangiogenic (AA) medicines, but recent evidence suggests that other medications may also be involved. Recognizing a broad range of drug-induced risk factors is important, notably in light of the increasing number of drugs associated with MRONJ. The primary objective of this review is to update and synthesize findings from the past 22 years (2003 to April 2025) regarding medications associated with MRONJ, expanding beyond the traditional AR and AA drugs to include more recent and developing therapeutic classes. This review combines findings from recent literature, including studies on AR and AA medications, as well as other drug classes, such as targeted cancer therapies and immunomodulatory agents. This review provides updated insights into MRONJ for healthcare practitioners and dentists, emphasizing the significance of risk assessment, early recognition, and multidisciplinary management to improve patient care and outcomes. Given its potential to cause significant morbidity and complicate dental and medical treatments, MRONJ presents a critical concern in clinical practice, underscoring the need for heightened awareness among healthcare professionals.

Keywords: antiangiogenic drugs; antiresorptive agents; drug-induced osteonecrosis; medication-related osteonecrosis of the jaw (mronj); mronj prevention.

Figure 1. PRISMA 2020 flow diagram of the study selection process

PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses Image source: Page et al. (2021) [5]; Creative Commons Attribution (CC BY) license

Figure 2. Comparison of normal bone remodeling vs. effects of BPs

The left panel shows a balanced cycle of normal bone remodeling, in which osteoblasts promote the formation of new bone while osteoclasts resorb existing bone. The right panel illustrates the impact of BPs, which suppress osteoclast activity and lead to decreased bone resorption and impaired remodeling. Prolonged suppression of osteoclast function can result in excessive bone mineralization, reduced bone turnover, and an increased risk of MRONJ. BP, bisphosphonate; MRONJ, medication-related osteonecrosis of the jaw Image created using Linearity Curve. Credit: Nasimeh Baghalipour. Adapted from [8-10,41]

Figure 3. Comparison of normal bone remodeling vs. effects of denosumab

The left panel illustrates normal bone remodeling, where osteoclasts resorb bone, and osteoblasts facilitate new bone formation in a balanced cycle. The right panel shows the effect of denosumab, an mAb that inhibits RANKL. By blocking RANKL, denosumab inhibits osteoclast differentiation, activity, and survival, leading to decreased bone resorption. This disruption in bone remodeling can result in excessive bone density, poor healing, and an increased risk of MRONJ. mAb, monoclonal antibody; MRONJ, medication-related osteonecrosis of the jaw; RANKL, receptor activator of nuclear factor kappa-B ligand Image created using Linearity Curve. Credit: Nasimeh Baghalipour. Adapted from [11,12,42]

Figure 4. Comparison of normal bone remodeling vs. effects of AA agents

The left panel shows normal bone remodeling, where adequate vascularization supports osteoclast and osteoblast function, ensuring balanced bone resorption and formation. The right panel illustrates the effects of AA drugs, which inhibit VEGF and other pathways essential for angiogenesis. Decreased blood vessel formation impairs bone turnover, delays healing, and compromises bone regeneration. This vascular disruption increases susceptibility to MRONJ. AA, antiangiogenics; MRONJ, medication-related osteonecrosis of the jaw; VEGF, vascular endothelial growth factor Image created using Linearity Curve. Image Credit: N. Baghalipour. Adapted from [13,14,15,16,44]