Background: Charcot Neuroarthropathy (CN) is an under recognised but potentially devastating complication arising from peripheral neuropathy (PN). Now that Diabetes Mellitus (DM) is the leading cause of PN, its incidence is increasing. Pathophysiology is marked by progressive and destructive inflammation of soft tissue and bone, involves acute and chronic phases, and with increased morbidity and mortality. Current therapies are complex & costly & associated with poor adherence and reduced quality of life. Despite the need, CN research is challenging to conduct & thus sporadic with prior studies failing to demonstrate effective treatments.
Aims & methodology: The RANK-Ligand monoclonal antibody Denosumab moderates osteoclastic activity at a key point of bone metabolism. We propose that denosumab will reduce the duration of acute CN and in 2015 commenced a pilot study of denosumab for acute CN in people with diabetes. To our knowledge this is among the first study of its kind internationally.
Results: To date ten participants have enrolled with following characteristics: (mean) age 56yrs; 25% male; 90% T2D; duration 17yrs. Eight participants have 10 outcomes (mean change in temperatures) from Week 1 through to Week 12 available, which was significantly reduced (-3.4oC). Time taken to induce remission of acute CN was <9 weeks.
Additional clinical and demographic data will be presented.
Impact on clinical practice: If validated, these promising results suggest that a novel off-label use for denosumab will significantly reduce the duration of acute CN, thus improving clinical outcomes and quality of life for people with DM related CN and potentially also reduce CN's high health costs.
In some ways CN can be viewed as a proxy for diabetic foot disease in the wider diabetes community: a serious condition that is relatively under recognised and under treated. Trials such as this demonstrate the value of further research into CN.