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

Joel Willem Johan Lasschuit; Jacqueline Ruth Center; Jerry Richard Greenfield; Katherine Thuy Trang Tonks; Charcot Foot Quantitative Ultrasound and Denosumab Study (CRUSADES) Investigators

doi:10.1016/j.jdiacomp.2024.108718

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

J Diabetes Complications. 2024 Apr;38(4):108718. doi: 10.1016/j.jdiacomp.2024.108718. Epub 2024 Mar 5.

Authors

Joel Willem Johan Lasschuit¹, Jacqueline Ruth Center², Jerry Richard Greenfield³, Katherine Thuy Trang Tonks⁴; Charcot Foot Quantitative Ultrasound and Denosumab Study (CRUSADES) Investigators

Affiliations

¹ Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia; Clinical Diabetes, Appetite and Metabolism Lab, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia; St Vincent's Clinical Campus, School of Clinical Medicine, University of New South Wales, Sydney, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia. Electronic address: j.lasschuit@garvan.org.au.
² Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia; Skeletal Diseases Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia; St Vincent's Clinical Campus, School of Clinical Medicine, University of New South Wales, Sydney, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia. Electronic address: j.center@garvan.org.au.
³ Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia; Clinical Diabetes, Appetite and Metabolism Lab, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia; St Vincent's Clinical Campus, School of Clinical Medicine, University of New South Wales, Sydney, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia. Electronic address: j.greenfield@garvan.org.au.
⁴ Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia; Clinical Diabetes, Appetite and Metabolism Lab, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia; St Vincent's Clinical Campus, School of Clinical Medicine, University of New South Wales, Sydney, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia; School of Medicine, University of Notre Dame, 160 Oxford Street, Darlinghurst, New South Wales 2010, Australia. Electronic address: k.tonks@garvan.org.au.

PMID: 38490126
DOI: 10.1016/j.jdiacomp.2024.108718

Abstract

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.

Keywords: Bone health; Calcaneal quantitative ultrasound; Charcot foot; Denosumab; Diabetes mellitus; Randomised controlled trial.

Publication types

Randomized Controlled Trial
Multicenter Study
Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Bone Density
Denosumab / adverse effects
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Diabetic Foot* / complications
Diabetic Foot* / drug therapy
Female
Humans
Inflammation
Male
Middle Aged

Substances

Denosumab