Denosumab in patients with aneurysmal bone cysts: A case series with preliminary results

Abstract

Purpose:: Aneurysmal bone cyst (ABC) is a rare skeletal tumor usually treated with surgery/embolization. We hypothesized that owing to similarities with giant cell tumor of bone (GCTB), denosumab was active also in ABC.

Methods:: In this observational study, a retrospective analysis of ABC patients treated with denosumab was performed. Patients underwent radiologic disease assessment every 3 months. Symptoms and adverse events were noted.

Results:: Nine patients were identified (6 male, 3 female), with a median age of 17 years (range 14-42 years). Primary sites were 6 spine-pelvis, 1 ulna, 1 tibia, and 1 humerus. Patients were followed for a median time of 23 months (range 3-55 months). Patients received a median of 8 denosumab administrations (range 3-61). All symptomatic patients had pain relief and 1 had paresthesia improvement. Signs of denosumab activity were observed after 3 to 6 months of administration: bone formation by computed tomography scan was demonstrated in all patients and magnetic resonance imaging gadolinium contrast media decrease was observed in 7/9 patients. Adverse events were negligible. At last follow-up, all patients were progression-free: 5 still on denosumab treatment, 2 off denosumab were disease-free 11 and 17 months after surgery, and the last 2 patients reported no progression 12 and 24 months after denosumab interruption and no surgery.

Conclusions:: Denosumab has substantial activity in ABCs, with favorable toxicity profile. We strongly support the use of surgery and/or embolization for the treatment of ABC, but denosumab could have a role as a therapeutic option in patients with uncontrollable, locally destructive, or recurrent disease.

Keywords: Aneurysmal bone cyst; bone tumor; denosumab; receptor activator of nuclear factor-kappa B ligand.

Figure 1.

Blood-filled cavity separated by fibrous septa composed of spindle cells, inflammatory cells, multinucleated osteoclast-like giant cells, and fibroblast-like cells. Nuclear atypia is not present (a); gender distribution (b); age (c); tumor site (d).

Figure 2.

Denosumab-induced bone calcification on computed tomography scan (a, b) and contrast medium decrease on magnetic resonance imaging (c, d) in a 16-year-old boy with spine aneurysmal bone cyst. Baseline (a, c) and after 33 administrations of denosumab 120 mg (b, d).

Figure 3.

A 16-year-old girl with pelvic aneurysmal bone cyst presenting fluid–blood levels and contrast medium enhancement at baseline (a, c), both reduced after 9 administrations of denosumab (b, d).

Figure 4.

A 12-year-old boy presenting with ulnar aneurysmal bone cyst: fluid–blood levels and cortical disruption at baseline (a, c), responding after 6 administrations of denosumab (b, d).

Figure 5.

Biopsy of a distal tibia aneurysmal bone cyst in a 17-year-old girl pre-denosumab. (a) Abundant blood is present at periphery and giant cells in the context of high cellularity lesion rich in mononuclear cells in the central area. (b) Post-denosumab: disappearance of all mononucleated and multinucleated cells with trabecular and hyaline cells (denosumab-induced changes).