Effect of denosumab on inflammation and bone health in active Charcot foot: A phase II randomised controlled trial

Aims: We aimed to investigate the effect of denosumab on pedal bone health and clinical resolution in active Charcot foot (CN). Methods: This multicentre open-label phase 2 randomised controlled trial recruited adults with diabetes mellitus and active CN within 3 months of onset. Participants were randomised to standard care alone, or with denosumab 60 mg subcutaneously. Denosumab was administered at baseline and again at 6 months, unless foot temperature had normalised (i.e. <2 degree celsius compared to contralateral foot). Co-primary outcomes were change in calcaneal Stiffness Index and foot temperature normalisation over 18 months. Results: Twelve participants per group were analysed; mean age 58 +/- 11 years, 83 % male and 92 % had type 2 diabetes. Active CN duration was median 8 (IQR 7-12) weeks. Ninety-two percent were Eichenholtz stage 1 and 96 % involved the midfoot. After 1-month, median decline in Stiffness Index was less in the denosumab verses standard care group (0.5 [IQR -1.0 to 3.9] vs -2.8 [-8.5 to -1.0], p = 0.008). At 18-months, 92 % of the denosumab group attained foot temperature normalisation versus 67 % of the standard care group (p = 0.13). Conclusions: Denosumab ameliorated the early decline in calcaneal Stiffness Index associated with active CN. However, no difference in normalisation of foot temperature was observed.