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Denosumab for craniofacial fibrous dysplasia: duration of efficacy and post-treatment effects

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Abstract

Denosumab has been advocated as a potential treatment for the rare skeletal disorder fibrous dysplasia (FD); however, there is limited data to support safety and efficacy, particularly after drug discontinuation. We report a case of successful treatment of aggressive craniofacial FD with denosumab, highlighting novel insights into the duration of efficacy, surrogate treatment markers, and discontinuation effects. A 13-year-old girl presented with persistent pain and expansion of a maxillary FD lesion, which was not responsive to repeated surgical procedures or bisphosphonates. Pre-treatment biopsy showed high RANKL expression and localization with proliferation markers. Denosumab therapy was associated with improved pain, decreased bone turnover markers, and increased lesion density on computed tomography scan. During 3.5 years of treatment, the patient developed increased non-lesional bone density, and after denosumab discontinuation, she developed hypercalcemia managed with bisphosphonates. Pain relief and lesion stability continued for 2 years following treatment, and symptom recurrence coincided with increased bone turnover markers and decreased lesion density back to pre-treatment levels. This case highlights the importance of considering the duration of efficacy when treating patients with FD and other nonresectable skeletal neoplasms that require long-term management.

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Abbreviations

FD:

Fibrous dysplasia

RANKL:

Receptor activator of nuclear factor kappa-B ligand

CT:

Computed tomography

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Acknowledgements

REDCap electronic data capture tools and Biomedical Translational Research Informatics (BTRIS) electronic data system were used for data collection and management.

Funding

This research was supported by the Intramural Research Program of the NIH, NIDCR. This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research, the Colgate-Palmolive Company, and other private donors.

Author information

Authors and Affiliations

  1. Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    L.N. Raborn, M.T. Collins & A.M. Boyce

  2. Oral and Maxillofacial Surgery, University of Washington School of Dentistry, Seattle, WA, USA

    A.B. Burke

  3. Department of Pediatric Hematology Oncology, Massachusetts General Hospital, Boston, MA, USA

    D.H. Ebb

  4. Department of Oral & Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA

    L.B. Kaban

  5. Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Building 30, Room 228, MSC 4320, Bethesda, MD, 20892-4320, USA

    A.M. Boyce

Authors
  1. L.N. Raborn
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  2. A.B. Burke
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  3. D.H. Ebb
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  4. M.T. Collins
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  5. L.B. Kaban
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  6. A.M. Boyce
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Corresponding author

Correspondence to A.M. Boyce.

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Informed consent

The patient in this study was seen as part of a natural history study approved by the Investigational Review Board of the NIDCR, NIH (NCT00001727). Informed assent and consent were obtained from the patient and her guardians.

Conflict of interest

NIDCR receives support from Amgen, Inc for an investigator-sponsored study of denosumab for fibrous dysplasia (Alison Boyce, Michael Collins). Layne Raborn, Andrea Burke, David Ebb, and Leonard Kaban report no conflicts of interest.

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Raborn, L., Burke, A., Ebb, D. et al. Denosumab for craniofacial fibrous dysplasia: duration of efficacy and post-treatment effects. Osteoporos Int 32, 1889–1893 (2021). https://doi.org/10.1007/s00198-021-05895-6

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  • DOI: https://doi.org/10.1007/s00198-021-05895-6

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