Successful treatment of adult cherubism with a 60 mg denosumab 6-monthly regimen.

Abstract

Cherubism is a rare autosomal dominant skeletal dysplasia, affecting the maxilla and/or mandible. The condition typically has childhood onset, followed by progression until puberty, with subsequent regression. Cherubism lesions share histological features with giant cell tumor of bone, where high-dose monthly denosumab is an effective medical treatment. Therefore, high-dose denosumab has also been trialed in children with cherubism with positive outcomes. However, the role of denosumab in adult cherubism, particularly a lower dose and frequency, has not been established. We present the case of a 60-year-old man with cherubism, reviewed for a new 39 × 21 mm left mandibular lesion. The patient had multiple surgeries up to the age of 30 for tumors in the right maxilla and mandible. Given the impact of further surgery on his appearance and quality of life, the patient was referred to Endocrinology for consideration of medical therapy. His bone turnover markers were slightly elevated with normal calcium, phosphate, 25-OH vitamin D, and parathyroid hormone levels. A bone density scan showed lumbar spine osteopenia. He was commenced on 60 mg denosumab 6-monthly with excellent clinical and radiological responses over the next 30 months. The most recent CT mandible showed a sustained reduction in the lesion size, measuring 36 × 18 mm, with osteoid formation and improvement in cortical thinning. Surgery is no longer indicated. No adverse effects from denosumab were reported in the patient. This is the first study to report the efficacy and safety of a low-dose denosumab regimen in the management of cherubism. This treatment approach was able to prevent major surgery and minimize denosumab-related adverse effects. While the optimal treatment duration remains unclear, the patient will continue with 60 mg denosumab 6-monthly in the short-term given the favorable response. In summary, a low-dose denosumab regimen should be considered for patients with cherubism, particularly those with contraindications or preferences to avoid surgery.