# Toward a Precision Medicine Approach to Medication-Related Osteonecrosis of the Jaw

> **NIH NIH R56** · UNIVERSITY OF FLORIDA · 2021 · $336,967

## Abstract

There is a fundamental gap in understanding how certain individuals treated with antiresorptives such as
bisphosphonates and denosumab developed medication-related osteonecrosis of the jaw (MRONJ) while
others do not. Without this knowledge, it is difficult to use the antiresorptives in a safe manner. Our long term
research goal is to identify, validate and implement clinically useful biomarkers of MRONJ and ultimately, to
proactively provide a Precision Medicine approach for antiresorptive therapies while minimizing the risk of
MRONJ. Built upon compelling preliminary findings, our overall objectives are to further validate
pharmacogenomic markers that predispose patients to bisphosphonates-related ONJ, to identify genetic and
serum biomarkers for denosumab-related ONJ, and to create a predictive model for future clinical
implementation of a Precision Medicine strategy for antiresorptive therapies. Our central hypothesis is that
MRONJ is the result of interplay between genetic predisposition and drug exposure, and that because of their
differing mechanisms of action, the genetic predispositions for MRONJ linked to bisphosphonates and
denosumab differ. We have assembled a multidisciplinary team to carry out the following specific aims: 1).
Identify genetic variants associated with bisphosphonate-related ONJ. 2). Identify genetic and serum
biomarkers for denosumab-related ONJ. 3). Build and validate predictive models for MRONJ. This project is
significant because study proposed study will not only identify validated genetic and/or serum biomarkers for
MRONJ and advance the understanding of the pathophysiology of MRONJ but also have translational
importance in the antiresorptive treatments for a wide range of diseases. The proposed study is innovative
because: First, this is the first pharmacogenomic study for denosumab-related MRONJ. Second, using bone
turnover markers as biomarkers for MRONJ is novel. Third, Using RANK and RANKL-containing extracellular
vesicles as biomarkers is novel. Fourth, identifying biomarkers unique for BP-related vs. DEN-related MRONJ
for clinical implementation is novel. Lastly, we will not only use a commonly adopted method for risk prediction
analyses but also two advanced methods that are capable of considering non-linear and interaction effects. In
summary, we believe our proposed studies will identify biomarkers for MRONJ, enhance our understanding of
the underlying mechanisms of MRONJ development, and provide an opportunity to improve treatment of
osteoporosis and cancer patients needing antiresorptive therapy in a personalized manner.

## Key facts

- **NIH application ID:** 10427077
- **Project number:** 1R56DE030538-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Yan Gong
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $336,967
- **Award type:** 1
- **Project period:** 2021-09-07 → 2023-09-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427077

## Citation

> US National Institutes of Health, RePORTER application 10427077, Toward a Precision Medicine Approach to Medication-Related Osteonecrosis of the Jaw (1R56DE030538-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10427077. Licensed CC0.

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