Treatment of Central Giant Cell Granuloma with Denosumab Therapy in Two Patients

Denosumab is a human monoclonal antibody that is used to treat osteoporosis, bone metastases, multiple myeloma and giant cell lesions of bone. Central giant cell granulomas are rich in osteoclast-like giant cells that express the RANK ligand (Receptor Activator of Nuclear factor Kappa-B Ligand), precursors that express RANK and mononuclear cells that express RANKL.  Denosumab functions by binding RANKL which inhibits osteoclast activity and therefore osteoclast-mediated bone destruction. 

The goal of this presentation is to present a follow-up report on the treatment of an 8 year old female patient with an aggressive central giant cell granuloma that was treated with subcutaneous denosumab therapy and to present an adult patient currently under similar therapy for the past 10 months.  

Case #1

 An 8 year old female was referred to the Baylor Oral and Maxillofacial Surgery department for evaluation of a rapidly growing lesion in her anterior mandible.  Clinically the patient’s mandibular dentition was grossly mobile.  A cone beam CT showed a large, poorly defined multilocular radiolucent area in the anterior mandible with cortical expansion and displacement of adjacent roots.  Incisional biopsy revealed a central giant cell lesion.  Laboratory values ruled out hyperparathyroidism.

The patient was referred to a pediatric oncologist for evaluation and consideration of potential bisphosphonate or RANKL-inhibiting medication for treatment of her central giant cell granuloma.  After a course of subcutaneous administration of denosumab, the mandibular cortical expansion is resolving and the teeth have stabilized.  A cone beam CT demonstrated that the lesion had decreased in size and has displayed new bone trabeculae within lesion.  Histopathologic evaluation of the area reveals de novobone formation with no evidence of residual CGCG.

Case #2

 43 year old female was referred to Baylor Oral and Maxillofacial Surgery department for evaluation of a large radiolucency in the left posterior mandible.  Biopsy revealed a central giant cell granuloma. Laboratory values were reviewed and normal.  The patient was treated with multiple intralesional triamcinolone injections without any appreciable clinical or radiographic improvement.

After consultation with the patient’s medical oncologist, the decision was made to begin denosumab therapy.  After 6 months of therapy, a cone beam CT revealed considerable shrinkage in volume of the lesion and an increase in radiodensity.  The plan is to continue denosumab therapy for total of 10 months and to biopsy the area to microscopically evaluate the residual lesion.

Off- label use of denosumab therapy has shown promise in reducing the size and radiographic progression of the aggressive CGCG and allowing for maintenance of the patient’s native bone with no adverse effects.  Early biopsy results show maturing new bone formation developing within lesion after treatment with denosumab.

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