Introduction: Denosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand that strongly suppresses differentiation and function of osteoclasts. Cherubism is a rare autosomal dominant disorder characterized by symmetrical swelling of the mandible and the maxilla. In patients with cherubism, the bone is replaced by a fibrous granuloma containing multinucleated giant cells, which are differentiated into activated osteoclasts
Objective: To report efficacy and safety of a 6-month treatment with denosumab in a child with cherubism
Case report: The Japanese boy was firstly diagnosed as cherubism at 4.5 years of age because of bilateral swelling of the lower jaw and a family history of the same disorder in his father. A heterozygous hot spot mutation for cherubism in the SH3BP2 gene (c.1253C>G, p.Pro418Arg) was identified in the patient by Sanger sequencing. At 9 years of age, he was referred to us because of progressive swelling of the jaws and delayed permanent teeth eruptions. The panoramic radiographs and computed tomography revealed expansive multiple cystic formations of the mandible and the maxilla and buried multiple permanent teeth. Because surgical treatment seemed to be difficult, he underwent denosumab treatment, consisting of 8 doses of subcutaneous denosumab injections (120 mg/dose) at day 0, day 7, day 28, and every 4 weeks thereafter for 6 months. The 6-month treatment suppressed the expansion of the cystic lesions that were dramatically ossified. Not only a bone resorption marker (urine NTx/Cr) level but also a bone formation marker (BAP) level quickly decreased upon the treatment and gradually increased 4 months off treatment. Upon treatment, he developed mild asymptomatic hypocalcemia that was controlled quickly after replacement of alfacalcidol. His growth chart showed decreased growth rate during a period from the initiation of the treatment to 5 months after the discontinuation. Other side effects, such as bone necrosis, have not been observed in the patient.
Conclusions: The present case demonstrated for the first time the therapeutic potential of denosumab for treatment of cherubism, although adverse impacts, especially on childhood growth, remain obscure. Further studies are needed to establish the safe and effective protocol of denosumab treatment for children.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology