# Osteomucosal healing and immunity in medication-related osteonecrosis of the jaw

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $390,000

## Abstract

ABSTRACT
Medication-related osteonecrosis of the jaw (MRONJ) is a destructive, non-healing intraoral lesion that
preferentially occurs after long-term use of anti-resorptive medications (ARMs) such as bisphosphonates (BPs)
or denosumab (Dmab) used for treating osteoporosis or bone malignancy. MRONJ severely diminishes quality
of life, often causes debilitating pain, and imposes other significant health issues. Because so little is known
about MRONJ pathophysiology and current treatments are largely palliative, there is an urgent need to better
understand the underlying pathogenetic mechanisms and develop effective therapeutic modalities. During the
past decade, our interdisciplinary team has developed various MRONJ mouse models, results of which point to
dysregulation of osteomucosal immunity as the leading source of MRONJ pathophysiology. Our long-term
goal is to understand the basis of osteomucosal immunity in MRONJ pathophysiology and evaluate the use of
targeted immunotherapies to mitigate MRONJ prior to its clinical presentation. Guided by our previously
published studies as well as unpublished preliminary data, we hypothesize that MRONJ pathogenesis is
associated with altered osteomucosal immunity and immune cell plasticity via pathologic amplification of the IL-
36/IL-23/Th17 axis in the presence of inflammatory oral diseases and ARMs. The objectives of this proposal
are: 1) to define how IL-36 functions as an initiator MRONJ pathogenesis; 2) to delineate the bridging role of
IL-23 from IL-36 to augmenting Th17 pathogenicity in MRONJ; and 3) to determine the pathologic role of Th17
cells during MRONJ progression. Completion of our proposed studies will provide the foundational framework
to harness MRONJ via immunotherapy and interventions for future clinical uses.

## Key facts

- **NIH application ID:** 10870267
- **Project number:** 1R56DE033281-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Yousang Gwack
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2023-07-19 → 2025-07-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870267

## Citation

> US National Institutes of Health, RePORTER application 10870267, Osteomucosal healing and immunity in medication-related osteonecrosis of the jaw (1R56DE033281-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10870267. Licensed CC0.

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