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 °C 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.

Contribution of peripheral neuropathy to poor bone health in the feet of people with type 2 diabetes mellitus.

AIMS: To evaluate the impact of peripheral neuropathy on bone health in people with type 2 diabetes mellitus (T2DM). METHODS: Participants with T2DM were grouped according to the presence of peripheral neuropathy as assessed by vibration perception threshold (VPT). Recruitment ensured groups were balanced for age, sex and body mass index (BMI). Bone health was measured by calcaneal quantitative ultrasound (QUS) and compared between groups. Calcaneal QUS parameters were correlated across the cohort with VPT and other prespecified variables. RESULTS: Thirty-four participants (17 per group) were included with mean age 68 ± 12 years, 47% male, with median BMI 29.9 (IQR 26.9-32.7) kg/m2. The peripheral neuropathy group had significantly lower mean Stiffness Index (87 ± 12 versus 101 ± 16, p = 0.01), Speed of Sound (1542 ± 28 versus 1574 ± 34 m/s, p < 0.01), and a trend towards lower Broadband Ultrasound Attenuation (113 ± 10 versus 120 ± 12 dB/MHz, p = 0.07). Pedal bone health asymmetry was not a significant feature in those with peripheral neuropathy. All calcaneal QUS parameters correlated negatively with VPT, although significance of the relationship with Broadband Ultrasound Attenuation was nullified if controlled for diabetes duration or time on insulin. Broadband Ultrasound Attenuation showed independent negative correlation with diabetes duration. CONCLUSIONS: People with T2DM and peripheral neuropathy have poorer bone health as measured by calcaneal QUS than those without peripheral neuropathy, independent of age, sex and BMI.