Endocrine Abstracts

Aneurysmal bone cysts (ABCs) are rare pseudotumoral bone lesions with potential aggressive behavior due to the extensive destruction of surrounding bone. Besides surgery, denosumab has been investigated as a treatment for benign fibro-osseous lesions. As for ABCs, pediatric experience is limited, reporting mainly beneficial effects on lesions growth and associated pain. Some reports included well known side effects associated with denosumab, such as the rebound hypercalcemia at discontinuation. In addition, denosumab in young patients may affect both bone modeling and remodeling, even if consequences on the growing skeleton have not been characterized. We describe the case of an 8-year old boy diagnosed with a spinal ABC not accessible to surgery. Denosumab was administered subcutaneously weekly for 4 weeks and then monthly for one year, with optimal clinical response and calcification of the tumor. Six months after the discontinuation of denosumab, the patient developed severe hypercalcemia that required administration of a loop diuretic and intravenous infusion of zoledronic acid to restore normal serum calcium values. Because of tumor recurrence, denosumab was resumed at similar doses and intervals. After a few months, a new episode of hypercalcemia occurred while on denosumab tapering, 3 months after an injection. At this point, the tumor was stable, and denosumab was stopped. The parents and the patient gave their consent to share clinical data on the Clinical Patient Management System (CPMS), an IT platform for clinical consultations between European Reference Networks. The panel of experts from the BOND ERN and the ERN for rare endocrine disease met, and 6 monthly zoledronic acid infusions were initiated in order to control the rebound hypercalcemia post-denosumab therapy. To now, four infusions have been performed, allowing calcium levels to remain below the upper limit of normal. In parallel to rapid changes of mineral homeostasis, we observed an amplified bone remodeling in response to denosumab. After 1 year of treatment, the patient developed sclerotic metaphyseal bands visible on radiographs. Sclerotic lines partially vanished during wash-out periods or when the injections of denosumab were spaced. Moreover, the patient developed over the years of denosumab therapy lower limb deformities, i.e. genu valgum, which required bilateral epiphysiodesis. Our experience confirms the efficacy of denosumab in treating ABCs, and suggests the importance of monitoring systematically growth, limb deformities, and mineral homeostasis in children and adolescents receiving denosumab. In addition, this report highlights the support of ERNs in the management of patients affected with rare diseases.