Title Denosumab Can Be Prescribed as a First-Line Treatment for Large, Aggressive-Type Central Giant Cell Granuloma Lesions
Clinical Question For patients with central giant cell granuloma, does denosumab provide equivalent or superior lesion resolution and recurrence rate reduction when used as a first-line treatment, as compared to conventional surgical resection?
Clinical Bottom Line Denosumab should be considered with other first-line treatments of large, aggressive-type central giant cell granuloma lesions because, when compared to segmental mandibular resection, it has reduced comorbidity and demonstrated curative success. This is supported by one cohort study and multiple case reports in which denosumab treatments averaging at least 12 months resulted in successful treatment of central giant cell granulomas. This treatment protocol has not been standardized and requires further research, but it shows promise to reduce the comorbidities often associated with these patients.
Best Evidence  
PubMed ID Author / Year Patient Group Study type
(level of evidence)
29035698Bredell/20185 patientsRetrospective cohort study
Key resultsFive patients with an aggressive growth type of central giant cell granuloma were treated with a loading dose of denosumab followed by monthly treatments for 1 year. Most patients showed clinical resolution of the lesion after 1 year, while some required a longer treatment course; the authors do not recommend treatment of less than 12-18 months because relapse can occur. Due to the significant systemic effects of denosumab, the authors also do not recommend using this regimen for small lesions that could be treated with a minimally invasive surgical technique.
25262402Naidu/20142 patientsCase report
Key resultsTwo patients diagnosed with central giant cell granuloma received nonsurgical therapy with monthly subcutaneously administered denosumab. After 4-6 months of treatment, CBCT evaluation showed considerable increases in radiodensity. Continued therapy revealed lesion shrinkage and resolution of facial asymmetry in both cases. Denosumab therapy was discontinued after incisional biopsy results showed no evidence of residual giant cell granuloma (9 months of denosumab treatment in one case and 18 months in the other). Follow-up CBCT scans taken at 6-month intervals showed continued resolution.
Evidence Search "denosumab"[All Fields] AND "central giant cell granuloma"[All Fields] denosumab[Title] AND central[Title] AND giant[Title] AND cell[Title] AND granuloma[Title]
Comments on
The Evidence
Validity: Evidence shows curative success of central giant cell granuloma with denosumab in numerous case reports, but currently there does not exist any systematic reviews or higher-level evidence to support this relatively new treatment modality. Therefore, case selection is important and, based on existing evidence, denosumab should be considered only for large, aggressive lesions. Perspective: Based on the cohort and case reports denosumab is a reasonable alternative treatment option to segmental resection for large central giant cell granuloma lesions. While there is risk of medication-related osteonecrosis of the jaw (MRONJ) when doing surgery during denosumab treatments, the risk after treatment is much less than with bisphosphonates. Denosumab is a monoclonal antibody, which is different than the bisphosphonate class of medications, which are deposited in bone with a potential half-life of more than 10 years. Denosumab reversibly binds to RANKL on osteoblasts, which allows for its antiresorptive effects to dissipate within 6 months of the discontinuing the drug.
Applicability Central giant cell granuloma is a rare disease of bone destruction that typically occurs in patients under 30 years of age. Aggressive subtypes are usually larger and occur at a younger age on initial presentation. They also have a higher rate of recurrence when treated with surgical curettage. Surgical resection is a successful treatment in removing large central giant cell granulomas, but this treatment has high esthetic and functional morbidity. Evidence, primarily in the form of case reports, has shown denosumab to be a successful curative treatment for large central giant cell granulomas and a potential first-line treatment in patients where segmental resection would otherwise be indicated. Risks of denosumab include, but are not limited to, pain in extremities and poor wound healing when surgical intervention occurs during denosumab therapy (stage II medicine-related osteonecrosis of the jaw). Duration of denosumab treatment and method of monitoring is variable at this time with recommendations of at least 1 year of monthly treatments. Monitoring methods include CBCT, CT, PET-CT or MRI. Other pharmacological treatments include intralesional corticosteroids, intranasal calcitonin spray, IFN-alpha, and bisphosphonates. Long-term follow-up is necessary to find recurrences in these patients.
Specialty (Oral Medicine/Pathology/Radiology) (Oral Surgery)
Keywords Central giant cell granuloma, denosumab
ID# 3360
Date of submission 12/03/2018
E-mail wendtt@livemail.uthscsa.edu
Author Tiffany J. Wendt, DDS
Co-author(s) e-mail
Faculty mentor Ryan R. Sheridan, DMD, MS
Faculty mentor e-mail ryan.r.sheridan.mil@mail.mil
Basic Science Rationale
(Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?)
None available
Comments and Evidence-Based Updates on the CAT
None available