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.

Reliability of a Three-Dimensional Wound Camera and Correlation With Routine Ruler Measurement in Diabetes-Related Foot Ulceration.

BACKGROUND: In an era of increasing technology and telehealth utilization, three-dimensional (3D) wound cameras promise reliable, rapid, and touch-free ulceration measurements. However, reliability data for commercially available devices in the diabetes foot service setting is lacking. We aimed to evaluate the reliability of diabetes-related foot ulceration measurement using a 3D wound camera in comparison to the routinely used ruler and probe. METHOD: Participants were prospectively recruited from a tertiary interdisciplinary diabetes foot service. Ulcerations were measured at each visit by two blinded observers, first by ruler and probe, and then using a 3D wound camera twice. Reliability was evaluated using intraclass correlation coefficients (ICC). Measurement methods were compared by Pearson correlation. RESULTS: Sixty-three ulcerations affecting 38 participants were measured over 122 visits. Interobserver reliability of ruler measurement was excellent for estimated area (ICC 0.98, 95% CI 0.97-0.98) and depth (ICC 0.93, 95% CI 0.90-0.95). Intraobserver and interobserver reliability of the 3D wound camera area was excellent (ICC 0.96, 95%CI 0.95-0.97 and 0.97 95% CI 0.96-0.98, respectively). Depth was unrecordable in over half of 3D wound camera measurements, and reliability was inferior to probe measurement. Area correlation between methods was good (R = 0.88 and 0.94 per observer); however, depth correlation was poor (R = 0.49 and 0.65). CONCLUSIONS: 3D wound cameras offer practical advantages over ruler-based measurement. In diabetes-related foot ulceration, the reliability and comparability of area measurement was excellent across both methods, although depth was more reliably obtained by the probe. These limitations, together with cost, are important considerations if implementing this technology in diabetes foot care.