Impact of Denosumab on Lower Extremity Surgery Rates in Charcot Foot

Research Type: Level 3 - Retrospective cohort study, Case-control study, Meta-analysis of Level 3 studies Introduction/Purpose: Charcot foot is a catastrophic joint disease usually associated with diabetic peripheral neuropathy. The most established treatment for Charcot foot is the total contact cast (TCC), which stabilizes and offloads the foot. Failure of this treatment can necessitate surgical correction, including ostectomy, external fixation, beaming, and amputation. Denosumab is an anti-RANKL monoclonal antibody approved to treat osteoporosis, but it also appears to preserve joint strength and increase remission rates in Charcot patients when used with TCC. The aim of this study is to identify the impact of denosumab use on rates of amputation, excision, arthrodesis, and reconstruction procedures of the foot in patients with Charcot. We hypothesize that denosumab treatment is associated with decreased rates of these lower extremity surgeries in Charcot patients. Methods: De-identified health records from 74 health organizations were obtained from the TriNetX US Collaborative Network for this retrospective cohort study. This study compared patients older than 18 years of age in two groups: Charcot foot without denosumab treatment and Charcot foot with denosumab treatment. Propensity score matching (PSM) accounted for some confounding variables, including age, sex, race, comorbid conditions, rheumatoid arthritis, vitamin D deficiency, and osteoporosis diagnoses. Following diagnosis with Charcot foot, patient risk ratios (RR) and p-values were calculated with 95% confidence intervals for amputation, excision, arthrodesis, and repair/revision/reconstruction procedures of the foot and toes. Additionally, Kaplan-Meier (KM) analyses estimated time-dependent risks in each group with significance set at p< 0.05. Results: PSM provided a sample size of 639 between the denosumab and non-denosumab groups with balanced age, sex, race, and comorbid conditions. Patients in the denosumab group were associated with a significantly lower frequency of foot and toe excision procedures compared to the non-denosumab group (1.958% vs. 4.819%, p=0.0040, RR=2.462, CI=1.304-4.648). Additionally, patients with denosumab treatment had a decreased frequency of arthrodesis procedures of the foot and toe (1.657% vs. 4.518%, p=0.0026, RR=2.727, CI=1.378-5.396). However, there was no significant difference between the two groups in amputation (3.313% vs. 5.12%, p=0.1013, RR=1.545, CI=0.914-2.614) or repair/revision/reconstruction procedures of the foot and toe (2.108% vs. 2.259%, p=0.8511, RR=1.071, CI=0.521-2.202). Conclusion: These data suggest that denosumab usage is associated with a lower frequency of foot and toe excision and arthrodesis procedures in patients with Charcot foot. Denosumab had no significant impact on foot and toe amputation or repair/revision/reconstruction. This is the first retrospective cohort study on the impact of denosumab on surgery rates in patients with Charcot foot. These results should motivate further investigation into denosumab as a potential therapeutic tool against Charcot foot, as it could potentially reduce the need for surgical intervention in patients with this disease. Table 1: Comparison of Foot and Toe Amputation, Excision, Arthrodesis, and Repair/Revision/Reconstruction procedures in Charcot Foot with and without Denosumab Treatment