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OBJECTIVE: To compare risks of lower-extremity amputation between patients with Charcot arthropathy and those with diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A retrospective cohort of patients with incident Charcot arthropathy or diabetic foot ulcers in 2003 was followed for 5 years for any major and minor amputations in the lower extremities. RESULTS: After a mean follow-up of 37 ± 20 and 43 ± 18 months, the Charcot and ulcer groups had 4.1 and 4.7 amputations per 100 person-years, respectively. Among patients <65 years old at the end of follow-up, amputation risk relative to patients with Charcot alone was 7 times higher for patients with ulcer alone and 12 times higher for patients with Charcot and ulcer. CONCLUSIONS: Charcot arthropathy by itself does not pose a serious amputation risk, but ulcer complication multiplicatively increases the risk. Early surgical intervention for Charcot patients in the absence of deformity or ulceration may not be advisable.

BackgroundCharcot arthropathy (CN) can ultimately lead to limb loss despite appropriate treatment. Initial conservative treatment is the accepted treatment in case of a plantigrade foot. The aim of this retrospective study was to investigate the mid- to long-term clinical course of CN initially being treated conservatively, and to identify risk factors for reactivation and contralateral development of CN as well as common complications in CN.MethodsA total of 184 Charcot feet in 159 patients (median age 60.0 (interquartile range (IQR) 15.5) years, 49 (30.1%) women) were retrospectively analyzed by patient chart review. Rates of limb salvage, reactivation, contralateral development and common complications were recorded. Statistical analysis was performed to identify possible risk factors for limb loss, CN reactivation, contralateral CN development, and ulcer development.ResultsMajor amputation-free survival could be achieved in 92.9% feet after a median follow-up of 5.2 (IQR 4.25, range 2.2–11.25) years. CN recurrence occurred in 13.6%. 32.1% had bilateral CN involvement. Ulcers were present in 72.3%. 88.1% patients were ambulating in orthopaedic footwear without any further aids. Presence of Diabetes mellitus was associated with reactivation of CN, major amputation and ulcer recurrence. Smoking was associated with ulcer development and necessity of amputations.ConclusionsWith consistent conservative treatment of CN with orthopaedic footwear or orthoses, limb preservation can be achieved in 92.9% after a median follow-up of 5.2 years. Patients with diabetic CN are at an increased risk of developing complications and CN reactivation. To prevent ulcers and amputations, every effort should be made to make patients stop smoking.Level of EvidenceIII, long-term retrospective cohort study

Aims/hypothesis We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study. Methods Clinicians managing cases of acute Charcot foot in the UK and Ireland between June 2005 and February 2007 were invited to register anonymised details on a secure website. Results A total of 288 cases (age 57.0 ± 11.3 years [mean ± SD]; 71.2% male) were registered from 76 centres. Of these, 36% of patients recalled an episode of relevant trauma in the preceding 6 months, while 12% had had surgery to the affected foot. In 101 (35%) cases, ulceration was present at registration and 20% of these had osteomyelitis. Non-removable off-loading devices were used at presentation in 35.4% of cases, with removable off-loading used in 50%. Data on resolution were available for 219 patients. The median time to resolution was 9 months in patients whose initial management included the use of non-removable off-loading, compared with 12 months in the remainder ( p  = 0.001). Bisphosphonates were administered intravenously in 25.4% and orally in 19.4% of cases. The median time to resolution in patients who received bisphosphonates was 12 months and was longer than in those who did not (10 months, p  = 0.005). Conclusions/interpretation The median time to resolution was longer than in earlier series. Although limited by being observational and non-randomised, these data suggest that the use of non-removable off-loading at presentation may shorten the time to resolution. They provide no evidence to indicate that the use of bisphosphonates is beneficial.

Charcot neuroarthropathy (CN) is an inflammatory arthropathy associated with bony destruction, dislocation, and deformity in patients with neuropathy. Surgical procedures involving foot and ankle in CN for deformity correction have been shown to result in high rate of complications. The purpose of this study was to compare post-operative outcomes and assess odds of complication after ankle arthrodesis among patients with diabetes-related Charcot neuroarthropathy, non-Charcot patients with diabetes, and non-Charcot patients without diabetes. The PearlDiver Patient Records Database was queried for patients who underwent ankle fusion and maintained at least one year of post-operative follow-up. The following post-operative complications were assessed among groups: overall nonunion and amputation, one-year nonunion, amputation, and hardware removal, 90-day and 30-day surgical site infection, dehiscence, acute kidney injury, and pneumonia, and 90-day myocardial infarction and deep vein thrombosis. The odds and prevalence of each complication for each group were assessed and compared. Higher rates of amputation (OR 3.43, CI 2.89–4.06), hardware removal (OR 1.63, CI 1.45–1.83), wound dehiscence (OR 1.75, CI 1.44–2.13), acute kidney injury (OR 2.87, CI 2.32–3.54), pneumonia (OR 1.53, CI 1.13–2.07), and surgical site infection (OR 2.46, CI 2.12–2.85), were observed in patients with diabetes-related CN compared to non-Charcot patients with diabetes. In patients without CN, higher rates of nonunion (OR 1.38, CI 1.19–1.61), amputation (OR 2.26, CI 1.74–2.93), surgical site infection (OR 1.57, CI 1.30–1.90), and acute kidney injury (OR 1.57, CI 1.18–2.09) were observed in patients with diabetes compared to patients without diabetes. Time to hardware removal was significantly shorter in diabetes-related Charcot patients compared to non-Charcot patients without diabetes (368.0 ± 446.7 vs 438.5 ± 487.5 days, P < 0.001). Patients with diabetes demonstrated increased odds of nonunion, amputation, surgical site infection, and acute kidney injury compared to patients without diabetes. In the population of patients with diabetes, odds of most of these complications were further increased with the addition of Charcot diagnosis compared to patients without diabetes. Other local and multisystemic medical conditions, including pneumonia and wound dehiscence, also demonstrated increased odds in patients of CN. Level of evidence: Cohort study; Level of evidence, 3. •Higher rates of post-operative complications were observed in diabetes-related Charcot patients compared to non-Charcot patients with diabetes•In patients without Charcot neuroarthropathy, higher rates of certain complications were observed in patients with diabetes•In the population of patients with diabetes, odds of most complications were further increased with the addition of Charcot diagnosis

BackgroundFailed conservative treatment and complications are indications for foot reconstruction in Charcot arthropathy. External fixation using the Ilizarov principles offers a one-stage procedure for deformity correction and resection of osteomyelitic bone. The aim of this study was to determine whether external fixation with an Ilizarov ring fixator leads reliably to walking ability.Materials and methods29 patients treated with an Ilizarov ring fixator for Charcot arthropathy were retrospectively analyzed. Radiologic fusion at final follow up was assessed separately on conventional X-rays by two authors. The association between walking ability and the presence of osteomyelitis at the time of reconstruction, and the presence of fusion at final follow up was investigated using Fisher’s exact test.ResultsMean follow up was 35 months (range 5.3–107) months; mean time of external fixation was 113 days. Ten patients (34.5%) reached fusion, but 19 did not (65.5%). Two patients needed below knee amputation. 26 of the remaining 27 patients maintained walking ability, 23 of those without assistive devices. Walking ability was independent from the presence of osteomyelitis at the time of reconstruction and from the presence of fusion.ConclusionFoot reconstruction with an Ilizarov ring fixator led to limb salvage in 93%. The vast majority (96.3%) of patients with successful limb salvage was ambulatory, independent from radiologic fusion, and presence of osteomyelitis at the time of reconstruction. These findings encourage limb salvage and deformity correction in this difficult-to-treat disease, even with underlying osteomyelitis.

Bone in diabetes mellitus is characterized by an altered microarchitecture caused by abnormal metabolism of bone cells. Together with diabetic neuropathy, this is associated with serious complications including impaired bone healing culminating in complicated fractures and dislocations, especially in the lower extremities, so-called Charcot neuroarthropathy (CN). The underlying mechanisms are not yet fully understood, and treatment of CN is challenging. Several in vitro and in vivo investigations have suggested positive effects on bone regeneration by modifying biomaterials with sulfated glycosaminoglycans (sGAG). Recent findings described a beneficial effect of sGAG for bone healing in diabetic animal models compared to healthy animals. We therefore aimed at studying the effects of low- and high-sulfated hyaluronan derivatives on osteoclast markers as well as gene expression patterns of osteoclasts and osteoblasts from patients with diabetic CN compared to non-diabetic patients with arthritis at the foot and ankle. Exposure to sulfated hyaluronan (sHA) derivatives reduced the exaggerated calcium phosphate resorption as well as the expression of genes associated with bone resorption in both groups, but more pronounced in patients with CN. Moreover, sHA derivatives reduced the release of pro-inflammatory cytokines in osteoclasts of patients with CN. The effects of sHA on osteoblasts differed only marginally between patients with CN and non-diabetic patients with arthritis. These results suggest balancing effects of sHA on osteoclastic bone resorption parameters in diabetes.

Syringomyelia is an important etiology of Charcot arthropathy of the elbow. We present five interesting patients, along with a systematic literature review summarizing the clinical profile and management of syringomyelia-induced Charcot arthropathy of the elbow. PUBMED, SCOPUS, EMBASE, and Science Direct databases were screened for English articles published between 1980 and 2022 using the search query: “Syringomyelia” AND “elbow” AND (“arthropathy” OR “neuropathic” OR “Charcot”). Articles without full text and/or lack of conclusive evidence of elbow arthropathy due to syringomyelia were excluded. The reference lists of the selected articles were reviewed to identify additional articles describing syringomyelia-induced Charcot arthropathy of the elbow. All five patients in the current series had elbow arthritis with variable motor weakness and dissociated sensory loss. The literature review included 31 reports (45 patients) and five patients from our center (n = 50). The median age at presentation was 45 (13–77) years. The median duration of arthropathy was 24 (0.5–180) months. Thirty-three patients had isolated elbow arthropathies. The other joints affected included the shoulder (n = 13), wrist (n = 7), metacarpophalangeal joints (n = 3), and interphalangeal joints (n = 1). Chiari malformations were present in 33 (66%) patients. Sensory deficits, motor deficits, and ulnar neuropathies were described in 36 (72%), 31 (62%), and 14 (28%) patients, respectively. Surgical decompression for syringomyelia was performed in 13 (26%) patients. The presence of dissociated sensory loss, with or without motor weakness, is key to the suspicion of syringomyelia-induced Charcot arthropathy of elbow. Chiari malformation and ulnar neuropathy are frequently associated with this condition. Key Points• Charcot arthropathy of elbow is not so uncommon as believed• Syringomyelia is an important etiology of Charcot arthropathy of elbow• Therefore, all patients with elbow arthropathy of unknown etiology must be evaluated for dissociative sensory loss• Chiari malformation and ulnar neuropathy are commonly associated with syringomyelia-induced Charcot arthropathy of elbow joint

Charcot neuroosteoarthropathy of the feet can induce severe instability and deformity with subsequent plantar ulceration leading to substantial disability or even amputation. Traditionally, nonoperative treatment is regarded as the primary option of treatment while surgery is restricted to treating complications or failure of nonoperative treatment. Failed nonoperative treatment essentially prolongs treatment period. We retrospectively reviewed 22 patients (26 feet) with midfoot (n = 9) or hindfoot (n = 17) neuropathy who underwent primary surgical reconstruction and reorientation arthrodesis due to manifest instability, nonplantigrade foot position, and deformity with overt (n = 8) or what we judged was impending ulceration (n = 9). The minimum followup was 0.5 years (mean, 2.7 years; range 0.5–7 years). All eight ulcers healed without recurrence of ulceration or manifestation of new ulcers during the followup period. We observed complications leading to further surgery in nine patients: five with perioperative hematoma and four with instability. AOFAS scores rose from a preoperative mean of 39 to 70 points (hindfoot cases) and from 51 points to 84 (midfoot cases). Early surgical reconstruction in high-risk patients can provide timely restoration of a plantigrade and stable foot and improved quality of life of the patient at complication rates comparable to those after secondary surgery following failed nonoperative treatment; however we emphasize we had no control group in this small case series for which we could compare nonoperative treatment. Level of Evidence: Level IV, therapeutic study (case series). See Guidelines for Authors for a complete description of levels of evidence.

Background Type 2 diabetes mellitus (T2DM) patients show a markedly higher fracture risk and impaired fracture healing when compared to non-diabetic patients. However in contrast to type 1 diabetes mellitus, bone mineral density in T2DM is known to be normal or even regionally elevated, also known as diabetic bone disease. Charcot arthropathy is a severe and challenging complication leading to bone destruction and mutilating bone deformities. Wnt signaling is involved in increasing bone mineral density, bone homeostasis and apoptotic processes. It has been shown that type 2 diabetes mellitus is strongly associated with gene variants of the Wnt signaling pathway, specifically polymorphisms of TCF7L2 (transcription factor 7 like 2), which is an effector transcription factor of this pathway. Methods Bone samples of 19 T2DM patients and 7 T2DM patients with additional Charcot arthropathy were compared to 19 non-diabetic controls. qPCR analysis for selected members of the Wnt-signaling pathway (WNT3A, WNT5A, catenin beta, TCF7L2) and bone gamma-carboxyglutamate (BGLAP, Osteocalcin) was performed and analyzed using the 2-ΔΔCt- Method. Statistical analysis comprised one-way analysis of variance (ANOVA). Results In T2DM patients who had developed Charcot arthropathy WNT3A and WNT5A gene expression was down-regulated by 89 and 58% compared to healthy controls ( p  < 0.0001). TCF7L2 gene expression showed a significant reduction by 63% ( p  < 0.0001) and 18% ( p  = 0.0136) in diabetic Charcot arthropathy. In all diabetic patients BGLAP (Osteocalcin) was significantly decreased by at least 59% ( p  = 0.0019). Conclusions For the first time with this study downregulation of members of the Wnt-signaling pathway has been shown in the bone of diabetic patients with and without Charcot arthropathy. This may serve as future therapeutic target for this severe disease.