Denosumab in active Charcot neuro-osteoarthropathy of the foot

Abstract

Objective: Active Charcot Neuro-osteoarthropathy (CN) is a rare and severe complication of peripheral neuropathy that leads to deformity and disability. No pharmacological treatment is available. Increased osteoclastic activity plays a central role in active CN, particularly via receptor activator of nuclear factor ligand (RANK-L). We aimed to describe clinical, morphological and metabolic imaging effects of denosumab, a fully human monoclonal anti- RANK-L antibody, in active CN.

Methods: In this open-label study, we included all consecutive patients with active refractory CN treated with denosumab in our tertiary center. Baseline and follow-up assessment included clinical examination, biological and imaging procedures (morphological and metabolic) before and after treatment.

Results: Seven patients were treated with denosumab between 2017 and 2020 and followed for a median of 16 months [6-39]. All patients clinically improved, 4 further relapsed after a median of 4 months [3-33]. Four patients were retreated with the same efficacy. Imaging follow-up available in 5 patients showed stability of structural damage (radiography) and a significant decrease of metabolic activity (FDG PET-CT) in 4 of them. No adverse event or hypocalcemia was observed.

Conclusion: In patients with refractory active CN, denosumab had a clinical effect, prevented bone and joint destruction, together with a metabolic effect, as assessed by FDG PET-CT. These results justify the conduction of a randomized controlled trial to assess the efficacy of denosumab in acute CN.

Keywords: Antiresorptive; Charcot neuroarthropathy; Denosumab; FDG PET-CT; Inflammation; RANK ligand.