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Clinical and Radiologic Response of Central Giant Cell Granuloma to Denosumab: A 6-Year Prospective Observational Study

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Abstract

Central giant cell granuloma (CGCG) is a rare lesion of the jaw occurring in young adults and adolescents. Surgery, the traditional mainstay of therapy, is associated with significant morbidity. Denosumab, a humanised monoclonal antibody to RANKL, is effective in a related entity, giant cell tumour of bone (GCTB), but experience in the more indolent CGCG is limited. This prospective observational study of all denosumab-treated CGCG at a tertiary referral centre (2015–2021) aimed to evaluate the safety, efficacy and recurrence risk using denosumab in CGCG at lower-frequency dosing than used for GCTB. All received standardised, time-limited courses of denosumab 120 mg with stepwise increase in dosing interval based on response. They were followed for up to 75 months using a radiation-minimising protocol: 3-monthly clinical, biochemical and radiological assessment (orthopantomograms, cone beam CT). Eight patients, median age 20.5 years [IQR 6], received 13 initial doses [IQR 10] of denosumab 120 mg. Radiologic response was seen after 5.5 doses [IQR 4.5]: ossification in all and size reduction in three. Recurrence occurred in four of seven completing therapy, observed 12 months post-cessation [IQR 6.5]. Larger baseline size, aggressive subtype and fewer than 12 initial doses were more common in the recurrence group. There was no osteonecrosis of the jaw. Hypocalcaemia occurred in one receiving modified dosing. This study represents the largest, most diverse cohort of denosumab-treated CGCG with the longest follow-up in literature. It demonstrates the efficacy of lower-frequency, time-restricted course of denosumab but highlights the risk of recurrence. Long-term follow-up is critical.

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Funding

No funding, grants or other support relevant to this manuscript was received.

Author information

Author notes

  1. Che-Jen Wang

    Present address: Dental and Maxillofacial Department, Prince of Wales Hospital, Sydney, NSW, Australia

Authors and Affiliations

  1. Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW, Australia

    Yoon Ji Jina Rhou, Minh Nguyen, Deborah Jane Holmes-Walker & Christian M. Girgis

  2. Department of Oral and Maxillofacial Surgery, Westmead Hospital, Sydney, NSW, Australia

    Che-Jen Wang, James Kim & Lydia Lim

  3. Department of Dental and Oral Surgery, Sydney Children’s Hospital, Randwick, Sydney, NSW, Australia

    Che-Jen Wang

  4. Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Sydney, NSW, Australia

    Joel A. Vanderniet & Craig F. Munns

  5. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

    Craig F. Munns, Deborah Jane Holmes-Walker & Christian M. Girgis

  6. Department of Anatomical Pathology, Douglass Hanly Moir, Sydney, NSW, Australia

    Hedley Coleman

  7. Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia

    Christian M. Girgis

Authors
  1. Yoon Ji Jina Rhou
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Contributions

YJR is responsible for the overall content. CMG, YJR, CFM and LL contributed to the study conception and design. Material preparation and data collection were performed by YJR, CJW, MN, JAV, HC, JK, LL, DJH and CMG. Data analysis was performed by YJR and CMG. The first draft of the manuscript was written by YJR, CMG and DJH, and all authors commented on and revised each version of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yoon Ji Jina Rhou or Christian M. Girgis.

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Conflict of interest

Craig F. Munns has previously been involved in an Amgen-sponsored clinical trial (not related to this manuscript). Christian M. Girgis has received an honorarium from Amgen for educational presentations on romosozumab. Yoon Ji Jina Rhou, Che-Jen Wang, Minh Nguyen, Joel A. Vanderniet, Craig F. Munns, Hedley Coleman, James Kim, Deborah Jane Holmes-Walker, Lydia Lim, and Christian M. Girgis have no other relevant financial or non-financial conflicts of interest to declare.

Human and Animal Rights and Informed Consent statement

Ethics approval was obtained from the Western Sydney Local Health District Human Ethics Committee and procedures followed were in accordance with the ethics standards of the committee and with the Helsinki Declaration. All data was collected as part of the participants' routine clinical management. Informed consent was obtained prior to photographing and the research participant has provided informed consent for publication of the images in Figures 4a and 4b.

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Rhou, Y.J.J., Wang, CJ., Nguyen, M. et al. Clinical and Radiologic Response of Central Giant Cell Granuloma to Denosumab: A 6-Year Prospective Observational Study. Calcif Tissue Int 110, 464–474 (2022). https://doi.org/10.1007/s00223-021-00935-z

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  • DOI: https://doi.org/10.1007/s00223-021-00935-z

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