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Pathology

Head & Neck

OMS and Other Dental Specialists

Session: Pathology and Head & Neck Track: Hot-off-the-Press and Abstract Session

GP1d - Pediatric MRONJ Risk With Denosumab and Bisphosphonates

Thursday, September 12, 2024
4:00 PM – 4:10 PM EDT
Location: Tangerine Ballroom WF2, Orange County Convention Center

    Oral Abstract Presenter(s)

  • RF

    Richard Foote

  • Sasha Lasky, BS

    Research Fellow
    Division of Plastic and Maxillofacial Surgery, Children's Hospital Los Angeles
    South Pasadena, California

    • Co-Author(s)

  • Tayla Moshal

    Research Fellow
    Division of Plastic and Maxillofacial Surgery, Children's Hospital Los Angeles
    Los Angeles, California

  • PS

    Pasha Shakoori, MD, DDS

    Plastic Surgery Resident
    Division of Plastic and Maxillofacial Surgery, Children’s Hospital Los Angeles
    Los Angeles, California

  • Idean Roohani, BS

    Research Fellow
    Division of Plastic and Maxillofacial Surgery, Children's Hospital Los Angeles
    Los Angeles, California

  • Marah Jolibois, MS (she/her/hers)

    Research Fellow
    Division of Plastic and Maxillofacial Surgery, Children's Hospital Los Angeles
    Los Angeles, California

  • Simon Youn, MD DDS

    Oral Maxillofacial Surgery Resident
    LA General Medical Center
    Los Angeles, California

  • MU

    Mark M. Urata, DDS, MD

    Plastic Surgeon Attending
    Division of Plastic and Maxillofacial Surgery, Children’s Hospital Los Angeles
    Los Angeles, California

  • Jeffrey A. Hammoudeh, DDS, MD

    Plastic Surgeon Attending
    Division of Plastic and Maxillofacial Surgery, Children’s Hospital Los Angeles
    Los Angeles, California

Abstract:

Background: Antiresorptive targeted cancer therapies, such as denosumab and bisphosphonates, are utilized in adults, but their application in pediatric cancer treatment is more recent.1,2 Side effects such as osteonecrosis of the jaw (ONJ) observed in adults have curtailed use of these medications in the pediatric population. This study assesses the incidence of ONJ, other side effects, and the indications for use of denosumab versus bisphosphonates in the pediatric population.

Methods: A retrospective cohort study of pediatric subjects who underwent index bisphosphonate or denosumab therapy at our institution from 2007 to 2023 was conducted. The independent variable was treatment with index bisphosphonate or denosumab therapy. Primary outcomes were incidence of bisphosphonate- and denosumab-related ONJ. Secondary outcomes included indications for bisphosphonate or denosumab use and additional side effects produced by either medication. ONJ risk factors, subject demographics, timing, duration, and cumulative dose of index medical therapy were abstracted. Descriptive statistics assessed ONJ incidence, risk factors, and indications for use of denosumab and bisphosphonates. Chi-squared tests compared the rates of side effects between subjects treated with bisphosphonates versus denosumab.

Results: A total of 178 subjects were included, of which 14 underwent denosumab therapy and 164 underwent bisphosphonate therapy. There were zero cases of ONJ across all subjects. The most common indication for treatment was adjuvant targeted therapy for aggressive tumors and malignancy (39.3%), followed by osteoporosis (14.6%), Duchenne’s muscular dystrophy (11.8%), and osteogenesis imperfecta (10.7%). Subjects treated with denosumab had significantly higher rates of hypercalcemia and severe bone pain than subjects treated with bisphosphonates, 28.6% vs 1.2% (P < .001) and 14.3% vs 0.00% (P < .001) respectively.

Conclusions: While invasive dental procedures should ideally be performed before antiresorptive treatment, our data suggests that bisphosphonates may be utilized safely in the pediatric population with very low concern for ONJ. Our data also demonstrated bisphosphonates may have a more tolerable side-effect profile than denosumab. We recommend utilizing bisphosphonates as first line therapy in children without the traditional risk of ONJ, while reserving denosumab for refractory cases. Future studies will help determine differences in efficacies and determine long-term side effects of these medications. References1. Bamias A, Kastritis E, Bamia C, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol. 2005;23(34):8580-8587.2. Kuroshima S, Sasaki M, Sawase T. Medication-related osteonecrosis of the jaw: A literature review. J Oral Biosci. 2019;61(2):99-104.

Mechanisms of Action of Denosumab and Bisphosphonates
A Comparison of Side Effects in Patients Treated with Bisphosphonates versus Denosumab
Malignancies and Aggressive Tumors Treated with Adjuvant Bisphosphonate or Denosumab Therapy