Charcot neuro-osteoarthropathy (CNO) is a destructive inflammatory condition of the bones and joints of the foot and ankle that occurs in people with diabetes and peripheral neuropathy. Left unrecognized, it can progress to fracture, collapse, fixed deformity, ulceration, and amputation. The 2023 International Working Group on the Diabetic Foot (IWGDF) guideline estimates that roughly 1.6 million people worldwide live with CNO, with about 160,000 new cases each year, and reports a pooled five-year mortality of approximately 29% in affected individuals (Wukich et al., 2024). This article summarizes what current evidence says about diagnosing and managing active CNO.
Recognizing Active Charcot Neuro-Osteoarthropathy
The IWGDF guideline advises clinicians to consider active CNO in any person with diabetes and neuropathy who presents with a red, warm, swollen foot with intact skin, compared with the opposite limb. Because the presentation can resemble infection, gout, or deep vein thrombosis, delayed recognition is common. A UK survey cited in the guideline found that about one-third of patients initially received suboptimal treatment.
Imaging and Temperature Assessment
Weight-bearing radiographs (anteroposterior, oblique, and lateral views) are the first-line imaging study. When radiographs appear normal but suspicion remains, the guideline gives a strong recommendation, based on moderate-certainty evidence, for magnetic resonance imaging (MRI), which is highly sensitive for early bone marrow edema and microfractures. CT, scintigraphy, or SPECT-CT may be used if MRI is unavailable or contraindicated. Infrared skin thermometry, comparing the affected and unaffected feet, is used to support diagnosis and monitoring, although the commonly cited 2°C difference threshold lacks rigorous validation. Blood markers such as C-reactive protein, erythrocyte sedimentation rate, white cell count, and alkaline phosphatase are not recommended for diagnosis because of insufficient accuracy.
Immobilization and Offloading: The Cornerstone of Treatment
The guideline strongly recommends starting offloading and immobilization as soon as active CNO is suspected, even before imaging confirms it. The preferred device is a non-removable total contact cast (TCC). If a TCC cannot be used, a non-removable knee-high walker is second choice, and a removable knee-high device is third. Below-ankle devices are not recommended because they provide inadequate immobilization. Crutches or walkers may be added to reduce load on the affected limb.
The importance of device choice is supported by clinical data. In the CADOM feasibility trial, Gooday and colleagues (2023) found that participants treated with a non-removable device reached remission sooner than those given a removable device (hazard ratio 0.285, p=0.012). The same study showed the human burden of the condition: nearly all participants reported pain and mobility problems, and about half scored above normal thresholds for anxiety and depression.
Determining Remission and Duration of Treatment
Active CNO typically takes several months to settle, and no single gold-standard test defines remission. The guideline suggests combining serial infrared thermometry of both feet, clinical assessment of edema, and radiographic evidence of consolidation. Immobilization is generally continued for four to six weeks after clinical signs have resolved. In CADOM, mean time to remission was 235 days with standard care plus temperature and clinical monitoring and 292 days in the serial-MRI arm, a difference that was not statistically significant (p=0.096). The authors concluded that a definitive randomized trial was feasible, but serial MRI has not yet been shown to shorten treatment.
Medications, Surgery, and Preventing Reactivation
Several drug therapies have been studied in the hope of accelerating bone healing. The IWGDF guideline strongly recommends against bisphosphonates, calcitonin, parathyroid hormone, and methylprednisolone for treating active CNO, citing moderate-certainty evidence of no clear benefit. Denosumab is also not recommended at present because evidence is limited. Vitamin D and calcium may be given according to national guidance during fracture healing.
Surgery is conditionally recommended for selected cases with intact skin, namely joint instability, deformity with a high risk of ulceration, or pain that is intractable despite casting. The guideline notes that high-quality evidence is limited and that surgery carries higher complication rates and upfront costs than offloading.
After remission, the guideline strongly recommends therapeutic footwear that accommodates foot shape and supports the ankle, and custom below-knee devices such as Charcot restraint orthotic walkers (CROW) or ankle-foot orthoses when deformity or instability is present. The accompanying systematic review of 37 studies (Raspovic et al., 2024) found no studies meeting its criteria on preventing reactivation, indicating an important gap in the literature.
Key Takeaways
Active CNO should be suspected in any neuropathic diabetic foot that is red, warm, and swollen with intact skin. Radiographs and, when needed, MRI support the diagnosis, and immobilization should begin without delay, preferably in a total contact cast. Remission is judged by a combination of temperature, edema, and radiographic findings rather than any single test. Current evidence does not support bisphosphonates or similar agents, and surgery is reserved for selected cases. Overall, the evidence base remains of low to moderate certainty, and well-designed trials are still needed.
References
- Wukich DK, Schaper NC, Gooday C, et al. Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023). Diabetes/Metabolism Research and Reviews. 2024.
- Raspovic KM, Schaper NC, Gooday C, et al. Diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus: a systematic review. Diabetes/Metabolism Research and Reviews. 2024.
- Gooday C, et al. A randomised feasibility study of serial magnetic resonance imaging to reduce treatment times in Charcot neuroarthropathy in people with diabetes (CADOM). Journal of Foot and Ankle Research. 2023.
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