RANKL Antibody (Danosumab) for Acute Charcot Neuro-osteoarthropathy Remission in Chronic Kidney Disease

Participants attending the outpatient diabetic foot facility of tertiary care hospital in North India were assessed for active CN. An active CN of the foot was considered in the presence of localised erythema, edoema, and a temperature differential of more than 20C compared to a similar location on the opposite foot. Participants were diagnosed with "active on chronic" CN if they met the requirements for active CN in the context of foot deformities suggestive of chronic CN (rocker bottom deformity). Those with self-reported diabetes or those who were already receiving treatment for diabetes, with an estimated glomerular filtration rate (eGFR) <60 ml/min/m2 (CKD-EPI equation) and more than 500 mg of urine protein/24 hours were considered as having diabetic CKD. Patients with active pedal ulcer, inactive charcot foot, peripheral vascular disease (ankle brachial index ABI <0.9), prior exposure to medications affecting bone metabolism particularly bisphosphonates, teriparatide, denosumab or steroids in the past 12 months, hypocalcemia, active malignancy, CKD on dialysis and pregnancy or lactating women were excluded. The study was conducted in accordance with the Declaration of Helsinki and its amendments, the International Conference on Harmonization Good Clinical Practice guidelines, and its applicable regulatory requirements. All participants provided their signed, fully informed consent and study protocol was approved by the institutional Ethics Committee ref INT/IEC/SPE-1664.

The foot temperature was determined by an infrared dermal thermometry [(FLIR Systems Inc, Orlando, USA) with a pixel resolution of 4800 (80*60), thermal sensitivity of 0.15 C, and a detection range of -20 C to 250 C] after 30 minutes of removing footwear or cast. X-ray and/or magnetic resonance imaging (MRI) were used to confirm the diagnosis of an active CN (3T scanner Siemens MagnetromVerio). The involved area of foot was classified anatomically for pattern of involvement using the Sanders-Frykberg classification. Clinical information was documented, including the duration of the symptoms, duration of diabetes, concomitant microvascular and macrovascular complications. Comprehensive neurological testing included vibration perception threshold (VPT>25 mV was considered abnormal) by biothesiometer-Vibrometer-VPT1 (Diabetik Foot Care, Madras Engineering Service, India), perception of 10-g monofilament at 5 standardised plantar locations, and ankle reflex.

Interventions:

Participants were randomly assigned in 1:2 ratio to receive either injection denosumab 60 gm (Group A) or equal volume of normal saline (Group B) subcutaneous over abdomen as a single dose (denosumab and normal saline were provided in similar looking syringe). The investigator administering the treatment, radiologist and the patient were blinded to treatment allocation. A conventional below knee, non-walking, non-removable fibreglass total contact cast (TCC) were provided to all participants irrespective of the group allocation for offloading.

Procedures: