Charcot Neuro-osteoarthropathy Research Articles

Charcot Neuro-Osteoarthropathy With Superimposed Osteomyelitis in a Nondiabetic Patient, as a Consequence of Cancer Chemotherapy: A MR-Monitored Case Report.

Charcot neuro-osteoarthropathy (CNO) is a manifestation of peripheral neuropathy as a chronic complication of diabetes mellitus but, less frequently, can be associated to other conditions such as alcoholism or neurotoxic therapies. An increasingly emerging cause of CNO is the use of oncological drugs which can cause neuropathic damage. The use of these therapies dramatically increased in recent years. CNO leads to a progressive degeneration of the foot's joints and to bone destruction and resorption which ends in deformities. These alterations in the foot's anatomy determine a high risk of ulceration, infection, and osteomyelitis. The superimposition of osteomyelitis on CNO increases the risk of major amputation, already high in patients suffering either from only CNO or osteomyelitis alone. We report the case of a 61-year old nondiabetic woman affected by CNO as a consequence of antiblastic therapy for breast cancer and the subsequent overlap of osteomyelitis, confirmed by magnetic resonance imaging. This case underlines how it is necessary to consider CNO as a possible complication of antiblastic therapy in the view of the severe consequences of missing its diagnosis.

Charcot Foot: An Update on Diagnosis, Treatment, and Areas of Uncertainty.

Charcot neuroosteoarthropathy (CN) is considered a rare complication of diabetic neuropathy. Due to its insidious mode of presentation, CN may be difficult to diagnose timely and a high index of suspicion is required from both, the diabetic patient (especially those with neuropathy) and their physicians for the early diagnosis and treatment to prevent major complications. We planned a narrative review and searched MEDLINE database to identify evidence regarding CN incidence, treatment options, and recent guidelines. As practitioners do not commonly treat CN, a characteristic clinical case is also presented. The available evidence for diagnosis and treatment remains of low quality. On the one hand, there is an urgent need for action to increase awareness of the disease in both practitioners and people with diabetes. On the other hand, prospective nationwide registries of patients with diabetic neuropathy will help clarify the prognostic factors that may predispose to this complication, and more randomized clinical trials are needed to identify whether medical treatment may improve CN outcomes. For the time being, offloading of the foot to stop the perpetuation of trauma, and inflammation, and importantly to arrest the progression to a deformed nonfunctional foot is the cornerstone of medical therapy of CN. Multidisciplinary assessment between diabetologists and radiologists is fundamental for prompt diagnosis. To avoid potentially deleterious delays in diagnosis and treatment, every physician should bear in mind that every patient with diabetic neuropathy presenting with a warm swollen foot should be treated as having CN until proven otherwise.

Genetic Signature for the Causation of Charcot Neuro-osteoarthropathy of Foot in Diabetes: A Systematic Review.

Charcot neuro-osteoarthropathy (CNO) is a complication of diabetes occurring in people with diabetic neuropathy with a prevalence of 0.5% to 1% that may culminate to foot deformity, amputation, and early mortality. However, it is not known why only certain patients with diabetic neuropathy develop CNO. Hence, early recognition of risk factors, timely diagnosis, and appropriate intervention of CNO is pertinent. Recent understanding of the pathophysiology of CNO has expanded to suggest the involvement of RANKL-OPG pathways. But pharmaco-therapeutic interventions targeting bone metabolism predominantly inhibiting RANKL were not found to be useful. Moreover, there are not enough markers to help identify patients with diabetes who are at a higher risk of developing CNO. Hence, we explored the literature in the present systematic review of mainly case-control studies to identify genetic factors that could help in understanding the pathophysiology and risk factors for the development of CNO. We could identify 7 relevant studies identifying single nucleotide polymorphism of OPG and RANK genes. There is an isolated study identifying alterations of micro RNA associated with RANKL-OPG pathway. Another study found epigenetic alterations by performing whole methylome sequencing in people with CNO compared to control. These genetic factors can be used as a diagnostic marker and their functional counterparts as targets for future therapeutic interventions. However, we found that literature is sparse on the genetic risk factors for CNO in people with diabetic neuropathy and there is still a lot of scope for future studies towards finding the molecular and genetic markers for CNO.

Rare complication of rheumatoid arthritis: Charcot Neuro-osteoarthropathy

BackgroundRheumatoid arthritis (RA) is an autoimmune disease.However, there are few cases of Charcot Neuro-osteoarthropathy (CN) caused by rheumatoid diseases in clinical reports. It is not easy to pay attention to the diagnosis of CN in the complications of rheumatoid disease, which greatly increases the probability of misdiagnosis and missed diagnosis. This case reported a rare complication of rheumatoid arthritis, Charcot arthritis, and the molecular mechanism and diagnosis and treatment of CN caused by RA were systematically discussed.Case presentationThe patient, a 79-year-old woman, was hospitalized due to bilateral shoulder pain, limited activity for half a year, aggravated for 4 months to the hospital. During this period, the symptoms did not improve after treatment with acupuncture and Chinese medicine. The patient was previously diagnosed with rheumatoid arthritis for more than 3 years and intermittent irregular use of methylprednisolone and methotrexate for 2 years. She had a history of osteoporosis. Physical examination: symmetrical malformed swelling of the finger joints of both hands; Bilateral supraspinatus and deltoid muscle atrophy, tenderness at the acromion, and attachment of the long head tendon of the biceps brachii were observed. The left Dugas test and the right Dugas test were positive.Blood test: anti-cyclic citrullinated peptide antibody (A-CCP) 33.10U/ml (normal range: 0-5RU/ml); antinuclear antibody quantification (ANA) 47.40AU/ml (normal range: Negative or < 32); anti-double stranded DNA IgG antibody quantification (dsDNA) 31.00 IU/ml (normal range: 0-100 IU/ml); D-Dimer 6.43 µg/ml (normal range: 0–0.5 mg/L); erythrocyte sedimentation rate (ESR) was 27 mm/h (normal range: < 20 mm/60 min). C-reactive protein (CRP) 39.06 mg/L(0.068-8 mg/L).MRI 3.0 T enhancement of bilateral shoulder joints, cervical spine and thoracic spine showed: 1.Large bone destruction, cartilage injury, multiple effusion, synovitis, obvious on the right side. 2.Intervertebral disc degeneration, cervical 3/4, 4/5, 5/6, 6/7 disc herniation, with cervical 3/4 obvious, posterior central herniation;ConclusionsRheumatoid arthritis complicated with Charcot's joint is rare. Clinically, patients with rheumatoid diseases should not ignore Charcot's joint complications because of rareness. Early blood inflammatory markers, neuro electrophysiology, and imaging MRI of rheumatoid CN are of great significance for the diagnosis of this mild or early neurovascular inflammation. Early diagnosis and treatment are helpful to prevent further joint injury. The clinical diagnosis, treatment, and molecular mechanism of osteolysis in RA and peripheral sensory nerve injury remain to be further revealed.

Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance.

Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings. This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem-Intervention/Indicator-Comparator-Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria. Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [18F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [18F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [18F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [18F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [18F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging. These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications.

Early Treatment of Acute Stage 0/1 Diabetic Charcot Foot Can Avoid Major Amputations at One Year.

Background: If unrecognized, Charcot neuro-osteoarthropathy (CNO) can be a devastating complication of diabetes. Methods: The aim of this retrospective study was to evaluate the outcomes in a cohort of diabetic patients diagnosed with active CNO managed in a tertiary level diabetic foot clinic (DFC). We included consecutive patients with active CNO, stage 0-1, according to the Eichenholtz-Shibata classification, who were referred from 1 January 2019 to 27 September 2022. Diagnosis of CNO was based on clinical signs and imaging (X-rays and magnetic resonance). All patients were completely offloaded by a total-contact cast (TCC) or removable knee-high device. Each patient was closely monitored monthly until CNO remission or another outcome. At 12 months of follow-up, the following outcomes were analyzed: remission, time to remission, major amputations (any above the ankle), and surgical indication. Results: Forty-three patients were included. The mean age was 57.6 ± 10.8 years; 65% were males and 88.4% had type 2 diabetes, with a mean duration of 20.6 ± 9.9 years. At baseline, 32.6% was affected by peripheral artery disease. Complete remission was recorded in 40/43 patients (93%), with a mean time to remission of 5.6 ± 1.5 months; major amputation and surgical indication occurred, respectively in 1/43 patients (2.3%) and 3/43 patients (7%). Conclusions: Early treatment of active Stage 0/1 CNO leads to high rates of remission and limb salvage.

Early diagnosis of Charcot neuro-osteoarthropathy using MRI and its effect on patient outcomes: A seven-year retrospective audit

BackgroundThere remains a paucity of research comparing the diagnostic and therapeutic outcomes between Magnetic Resonance Imaging (MRI) and x-ray modalities for Charcot neuro-osteoarthropathy CNO. This retrospective study investigates the use of offloading devices, duration of offloading and final footwear outcomes dependent on imaging at diagnosis. MethodsMedical records from a secondary hospital high-risk foot clinic in Perth, Western Australia, were systematically reviewed. Data collected included baseline medical history, location of CNO, Eichenholtz stage or Chantelau and Grutznel grade at diagnosis, type and duration of offloading, and final footwear outcomes. ResultsTwenty-eight patients met the inclusion criteria. All had diabetes and peripheral neuropathy. All patients received either an MRI (43%) or x-ray (57%) to confirm the diagnosis of active CNO. Five (17.9%) patients who were diagnosed on MRI had grade 0 CNO whilst 23 (82.1%) patients who were diagnosed on x-ray had stage 1 CNO. No statistical significance was found between the type and duration of offloading, resolution of CNO, footwear and transtibial amputation (TTA) outcomes across those diagnosed with MRI or x-ray. ConclusionNo statistical significance in patient outcomes was found between those diagnosed with grade 0 on MRI and those diagnosed with stage 1 on x-ray.

Charcot neuroarthropathy in persons with diabetes: It's time for a paradigm shift in our thinking.

The aim of this paper is to review the recent literature regarding the epidemiology and surgical management of Charcot neuro-osteoarthropathy (CNO). We propose that a fundamental change in the approach and assumptions regarding the historical treatment of active CNO should be considered. Although the true incidence and prevalence of CNO in the US population with diabetes are not known, we estimated the incidence to be 27,602 per year and the prevalence to be 208,880 persons. In persons with diabetes, the incidence of CNO is higher than that of prostate, lung, kidney, and thyroid cancer, and in the entire US population, the incidence of CNO is higher than that of multiple myeloma, soft tissue sarcoma, and primary bone sarcoma. In persons with diabetes, the incidence of CNO is higher than fractures of the femoral shaft, distal femur, tibia, talus, calcaneus and Lisfranc ligament injuries. Surgical techniques have evolved over the past half century, and surgery is the standard for treating displaced fractures and intra-articular injuries. Since CNO is a fracture, dislocation, or fracture dislocation in patients with neuropathy, why do we treat CNO differently? Elsewhere in the skeleton displaced osseous and ligament injuries are treated surgically. Based on the information presented in this manuscript, we suggest that it is time for a paradigm shift in the treatment of persons with CNO. While uncommon, CNO in persons with diabetes is not rare. Given the advances in surgical techniques, surgical intervention should be considered earlier in persons with CNO who are at risk for developing deformity related foot ulceration.

A new declaration for feet's sake: Halving the global diabetic foot disease burden from 2% to 1% with next generation care.

The 1989 Saint Vincent Declaration established a goal of halving global diabetes-related amputation rates. A generation later, this goal has been achieved for major but not minor amputations. However, diabetic foot disease (DFD) is not only a leading cause of global amputation but also of hospitalisation, poor quality of life (QoL) and disability burdens. In this paper, we review latest estimates on the global disease burden of DFD and the next generation care of DFD that could reduce this burden. We found DFD causes 2% of the global disease burden. This makes DFD the 13th largest of 350+ leading conditions causing the global disease burden, and much larger than dementia, breast cancer and type 1 diabetes. Neuropathy without ulcers and amputations makes up the largest portion of the global DFD burden yet receives the least DFD focus. Future care focussed on improving safe physical activity in people with DFD could considerably reduce the DFD burden, as this incorporates increasing physical fitness and QoL, while simultaneously decreasing ulceration and other risks. Charcot neuro-osteoarthropathy is more prevalent than previously thought. Most cases respond well to non-removable offloading devices, but surgical intervention may further reduce the considerable burden of these neuropathic fracture dislocations. Ischaemia is becoming more common and complex. Most cases respond well to revascularisation interventions, but novel revascularisation techniques, medical management and autologous cell therapies may hold the key to more cases responding in the future. We conclude that DFD causes a global disease burden larger than most conditions and existing guideline-based care and next generation treatments can reduce this burden. We suggest the World Health Organization and International Diabetes Federation declare a new goal: halving the global DFD burden from 2% to 1% within the next generation.

Features of organotopic remodeling of bone tissue and implanted osteoplastic material in Charcot neuro/osteoarthropathy

Introduction Despite the recognition of MRI as the gold diagnostic standard for Charcot arthropathy, there is evidence in the literature that MSCT is more informative for objective qualitative and quantitative diagnosis of the condition, primarily of the bone skeleton of the Charcot foot, in comparison with standard radiography. The sensitivity and specificity of these methods are different.Purpose To reveal the features of organotopic remodeling of bone tissue and implanted osteoplastic material in the course of midfoot and hindfoot subtotal defects management in Charcot neuro-osteoarthropathy.Materials and methods The analysis of bone tissue and implanted osteoplastic material density was carried out in a case series that included 11 patients with Charcot neuro-osteoarthropathy who underwent a two-stage procedure for bone defects in the hindfoot and midfoot with the Ilizarov apparatus. We studied CT and MRI scans and measured bone regenerate density before treatment, at the stages of transosseous osteosynthesis, and 3, 6, and 12 months after surgery.Results In all patients, varying increase in the amount and volume of bone tissue was visualized due to intensive periosteal bone formation along with the formation of bone ankylosis in the joints along combined with a consistent increase in the optical density of bone regenerates. The formation of the new bone tissue ran without the signs of lysis or sequestration. The conducted studies indicate that the sizes and architectonics of bone fragments are more differentiated in CT than in MRI scans.Discussion It is known that the bone, despite its high mineralization, continuously rebuilds, restores and adapts itself to certain functional conditions. This constant dynamic process of adaptive remodeling depends mostly on optimal blood supply, metabolic activity and the coordinated work of bone cell elements. The data obtained show angiogenesis in the compromised tissues in patients with Charcot foot and consistent remodeling of the graft into the new bone tissue.Conclusion The allobone in the composition of the combined bone graft does not reduce the likelihood of complete remodeling of the newly formed bone tissue. Higher bone density by filling in a bone defect with a graft differs from distraction regenerate that initially has low bone density. CT and MRI are highly effective and informative diagnostic methods for surgical treatment. In reconstructive interventions in the patients with Charcot foot under the conditions of transosseous osteosynthesis, preference among radiological study methods should be given to CT.

Grading Fractures on Foot and Ankle X-rays and MRI Scans in the Active Charcot Foot in Diabetes: How Strong Is the Agreement Between Modalities?

To compare X-ray and MRI as diagnostic tests of active Charcot neuro-osteoarthropathy (CNO) in diabetes. X-rays and MRI scans of 48 participants were rated for severity of fracture (0 = no fracture, 1 = fracture, 2 = collapse/fragmentation), and for absence/presence of bone marrow edema (BME) on MRI and absence/presence of bone injury on X-ray. The agreement between modalities was assessed with tests for symmetry, marginal homogeneity, and κ-coefficients. X-ray underscored MRI in grading fractures in the metatarsals (P = 0.05) and tarsals (P < 0.001) and reported as normal 79% of the bones with BME. The agreement between X-ray and MRI for grading severity of fracture was moderate to substantial (κ = 0.53; P < 0.001) and for detecting bone injury, slight to fair (κ = 0.17; P < 0.001). The significant underperformance of X-ray in the assessment of the hot, swollen foot in diabetes should be considered when confirming or refuting the diagnosis of active CNO.

Circular External Fixation as a New Offloading Standard of Treatment in Charcot Neuro-Osteoarthropathy Complicated by Midfoot Osteomyelitis: A Pilot, Prospective Case-Control Study.

After surgical treatment of Charcot neuro-osteoarthropathy (CNO) complicated by plantar ulcer and midtarsal osteomyelitis, offloading is mandatory to protect the surgical site. Total contact casting is, to date, the standard-of-care to offload the foot during the postoperative period. We have compared the application of external circular fixator, to the standard of care, with regard to surgical wound healing and time to healing. During the time period from January 2020 to December 2021, 71 consecutive patients admitted to our unit with diabetes and CNO complicated by plantar ulceration and midtarsal osteomyelitis were enrolled in our study. All patients were classified as stage 2, according to the Frykberg & Sanders classification. Wifi wound stage was W2 I0 FI2 in 43 of 71 patients (60.6%) and W2 I2 FI2 in 28 of 71 patients (39.4%). In cases where critical limb ischemia occurred, we performed an endovascular procedure to obtain patency in at least one of the tibial arteries. Localization of osteomyelitis was carried out with magnetic resonance imaging studies, and the degree of deformity was assessed using plain X-ray or computed tomography. A localized ostectomy through the ulceration was carried out with a fasciocutaneous flap to cover the surgical site. In 36 patients, an external circular fixator was applied intraoperatively (exfix+ group); the remaining 35 patients received fiberglass cast in the postoperative period (exfix- group). Complete healing of the surgical site was achieved in 36 of 36 patients in the exfix+ arm and in 22 of 35 in the exfix- arm (P < .02). Time to healing was 68 ± 28 days in exfix+ and 102 ± 88 days in exfix- (P = .05). Circular external frames should be considered as an effective offloading device that enhances the healing rate and reduces time to healing after surgical treatment of midfoot osteomyelitis in subjects affected by CNO.

Сравнение ортопедической реконструкции деформаций стоп при диабетической артропатии Шарко с консервативным лечением на стадиях 1-2 по классификации Eichenholtz

The objective was to evaluate the efficacy and safety of closed transosseous osteosynthesis in the treatment of patients with diabetic Charcot neuroosteoarthropathy at the acute radiographically positive stage (Eichenholtz 1-2) with hindfoot and midfoot deformity and immobilization using Total Contact Cast. Material and methods Eight patients of the treatment group underwent closed deformity correction and Ilizarov external fixation. The frame was removed with radiographic signs of consolidation and conservative methods of fixation and off-loading employed. The control group consisted of 11 patients who received outpatient conservative treatment with Total Contact Cast combined with crutches. Results The treatment length of surgical patients prior to the use of orthopaedic shoes was shorter than that of patients treated conservatively. Foot ulcers seen in the conservative group during the observation period were not detected in the surgical cases and were associated with the lack of deformity correction. Discussion The advantage of operative reconstruction includes more stable foot and lower risk of ulcers. Reduced rehabilitation period improves the patient's quality of life. Complications that developed in the treatment group were resolved and had no effect on the outcome. Conclusion Closed deformity correction using transosseous osteosynthesis can be an option for patients with diabetic Charcot neuroosteoarthropathy at the acute radiographically positive stage as compared to the conservative treatment.

Practical guidelines on the prevention and management of diabetes-related foot disease (IWGDF 2023 update).

Diabetes-related foot disease results in a major global burden for patients and the healthcare system. The International Working Group on the Diabetic Foot (IWGDF) has been producing evidence-based guidelines on the prevention and management of diabetes-related foot disease since 1999. In 2023, all IWGDF Guidelines have been updated based on systematic reviews of the literature and formulation of recommendations by multidisciplinary experts from all over the world. In addition, a new guideline on acute Charcot neuro-osteoarthropathy was created. In this document, the IWGDF Practical Guidelines, we describe the basic principles of prevention, classification and management of diabetes-related foot disease based on the seven IWGDF Guidelines. We also describe the organisational levels to successfully prevent and treat diabetes-related foot disease according to these principles and provide addenda to assist with foot screening. The information in these practical guidelines is aimed at the global community of healthcare professionals who are involved in the care of persons with diabetes. Many studies around the world support our belief that implementing these prevention and management principles is associated with a decrease in the frequency of diabetes-related lower-extremity amputations. The burden of foot disease and amputations is increasing at a rapid rate, and comparatively more so in middle to lower income countries. These guidelines also assist in defining standards of prevention and care in these countries. In conclusion, we hope that these updated practical guidelines continue to serve as a reference document to aid healthcare providers in reducing the global burden of diabetes-related foot disease.

Onset of an Active Charcot Foot in a Person with Longstanding Type 1 Diabetes and Normal Vibration Perception Threshold-A Case Report.

Charcot neuro-osteoarthropathy (CNO), or Charcot foot, is a disabling complication of diabetes, which is poorly understood and frequently overlooked. We describe an atypical presentation of an active Charcot foot in a woman with a long-standing type 1 diabetes who did not exhibit loss of protective sensation (sensate to a 10-gram monofilament) or loss of vibration sensation. These standard measures of large nerve fibre function ruled out "classical" neuropathy. However, additional testing showed reduced sweat gland function most likely related to degeneration of c-fibres (small fibre neuropathy). This case raises the awareness that in addition to the "textbook" description, in diabetes, Charcot foot can develop in individuals with "minimal" or "no signs" of clinical neuropathy. The onset of active Charcot foot should be suspected in every person with diabetes and history of trauma even when foot and ankle x-rays are normal. Offloading should be initiated until the diagnosis is proven otherwise.

Contralateral foot temperature monitoring during Charcot immobilisation: A systematic review.

Contralateral temperature difference (CTD) is a frequently used marker of healing in Charcot neuro-osteoarthropathy (CN). We aimed to determine whether there is a consistent approach to CTD measurement during healing and the decision-making process around cessation of immobilisation. Medline, Scopus, and Web of Science were searched until February 2022 for peer-reviewed studies using keywords, including (('arthropathy' OR 'osteoarthropathy' OR 'osteopathy' OR 'neuroarthropathy') AND 'Charcot' AND ('temperature')), which returned 789 results excluding duplicates. Included studies monitored CTD in those with active CN to (i) assess the healing process and (ii) assist in determining the transition from immobilisation. Thirty four studies in total (n=677 participants) were shortlisted and 19 were included after full paper review. Average CTD at presentation varied from 1.6 to 8.0°C with insufficient data to determine if CTD was proportional to severity of Charcot. Evidence of a relationship between CTD and radiographic or scintigraphy-based markers of healing varied depending on the methodology employed. Threshold CTD for the cessation of immobilisation ranged from <1°C to <2°C. Most frequently it was <2°C sustained for 2-3 visits. Temperature was monitored typically every 2-6weeks using handheld thermometry at CN site(s) after resting the feet for 15min. Device type, accuracy/reliability, and ambient temperature were rarely reported. Further research on CTD and radiographic and radiotracer markers is needed involving larger cohorts. Standardisation in reporting of thermometry device type, accuracy and reliability, foot resting times, and ambient temperature controls is essential to facilitate the comparison of studies, meta-analysis, and evaluation of different immobilisation interventions.

No Difference in Risk of Amputation or Frequency of Surgical Interventions Between Patients With Diabetic and Nondiabetic Charcot Arthropathy.

The cause of Charcot neuro-osteoarthropathy (CN) is diabetes in approximately 75% of patients. Most reports on the clinical course and complications of CN focus on diabetic CN, and reports on nondiabetic CN are scarce. No study, to our knowledge, has compared the clinical course of patients initially treated nonoperatively for diabetic and nondiabetic CN. Among patients with CN, are there differences between patients with diabetes and those without in terms of (1) the frequency of major amputation as ascertained by a competing risks survivorship estimator; (2) the frequency of surgery as ascertained by a competing risks survivorship estimator; (3) frequency of reactivation, as above; or (4) other complications (contralateral CN development or ulcers)? Between January 1, 2006, and December 31, 2018, we treated 199 patients for diabetic CN. Eleven percent (22 of 199) were lost before the minimum study follow-up of 2 years or had incomplete datasets and could not be analyzed, and another 9% (18 of 199) were excluded for other prespecified reasons, leaving 80% (159 of 199) for analysis in this retrospective study at a mean follow-up duration since diagnosis of 6 ± 4 years. During that period, we also treated 78 patients for nondiabetic Charcot arthropathy. Eighteen percent (14 of 78) were lost before the minimum study follow-up and another 5% (four of 78 patients) were excluded for other prespecified reasons, leaving 77% (60 of 78) of patients for analysis here at a mean of 5 ± 3 years. Patients with diabetic CN were younger (59 ± 11 years versus 68 ± 11 years; p < 0.01), more likely to smoke cigarettes (37% [59 of 159] versus 20% [12 of 60]; p = 0.02), and had longer follow-up (6 ± 4 years versus 5 ± 3 years; p = 0.02) than those with nondiabetic CN. Gender, BMI, overall renal failure, dialysis, and presence of peripheral arterial disease did not differ between the groups. Age difference and length of follow-up were not considered disqualifying problems because of the later onset of idiopathic neuropathy and longer available patient follow-up in patients with diabetes, because our program adheres to the follow-up recommendations suggested by the International Working Group on the Diabetic Foot. Treatment was the same in both groups and included serial total-contact casting and restricted weightbearing until CN had resolved. Then, patients subsequently transitioned to orthopaedic footwear. CN reactivation was defined as clinical signs of the recurrence of CN activity and confirmation on MRI. Group-specific risks of the frequencies of major amputation, surgery, and CN reactivation were calculated, accounting for competing events. Group comparisons and confounder analyses were conducted on these data with a Cox regression analysis. Other complications (contralateral CN development and ulcers) are described descriptively to avoid pooling of complications with varying severity, which could be misleading. The risk of major amputation (defined as an above-ankle amputation), estimated using a competing risks survivorship estimator, was not different between the diabetic CN group and nondiabetic CN group at 10 years (8.8% [95% confidence interval 4.2% to 15%] versus 6.9% [95% CI 0.9% to 22%]; p = 0.4) after controlling for potentially confounding variables such as smoking and peripheral artery disease. The risk of any surgery was no different between the groups as estimated by the survivorship function at 10 years (53% [95% CI 42% to 63%] versus 58% [95% CI 23% to 82%]; p = 0.3), with smoking (hazard ratio 2.4 [95% CI 1.6 to 3.6]) and peripheral artery disease (HR 2.2 [95% CI 1.4 to 3.4]) being associated with diabetic CN. Likewise, there was no between-group difference in CN reactivation at 10 years (16% [95% CI 9% to 23%] versus 11% [95% CI 4.5% to 22%]; p = 0.7) after controlling for potentially confounding variables such as smoking and peripheral artery disease. Contralateral CN occurred in 17% (27 of 159) of patients in the diabetic group and in 10% (six of 60) of those in the nondiabetic group. Ulcers occurred in 74% (117 of 159) of patients in the diabetic group and in 65% (39 of 60) of those in the nondiabetic group. Irrespective of whether the etiology of CN is diabetic or nondiabetic, our results suggest that orthopaedic surgeons should use similar nonsurgical treatments, with total-contact casting until CN activity has resolved, and then proceed with orthopaedic footwear. A high frequency of foot ulcers must be anticipated and addressed as part of the treatment approach. Level III, prognostic study.

Foot Osteomyelitis Location and Rates of Primary or Secondary Major Amputations in Patients With Diabetes.

Background:Diabetic foot osteomyelitis (DFO) often leads to amputations in the lower extremity. Data on the influence of the initial anatomical DFO localization on ultimate major amputation are limited.Methods:In this retrospective analysis, 583 amputation episodes in 344 patients (78 females, 266 males) were analyzed. All received a form of amputation in combination with antibiotic therapy. A multivariate logistic regression analysis with the primary outcome “major amputation” defined as an amputation above the ankle joint was performed. The association of risk factors including location of DFO, coronary artery disease, peripheral artery disease, neuropathy, nephropathy, and Charcot neuro-osteoarthropathy was analyzed.Results:Among 583 episodes, DFO was located in the forefoot in 512 (87.8%), in the midfoot in 43 (7.4%), and in the hindfoot in 28 episodes (4.8%). Overall, 53 of 63 (84.1%) major amputations were performed because of DFO in the setting of peripheral artery disease as primary indication. Overall, limb loss occurred in 6.1% (31/512) of forefoot, 20.9% (9/43) of midfoot, and 46.4% (13/28) of hindfoot DFO. Among these, 22 (41.5%) were performed as the primary treatment, whereas 31 (58.5%) followed previously failed minor amputations. Among this latter group of secondary major amputations, the DFO was localized to the forefoot in 23 of 583 (3.9%), the midfoot in 4 of 583 (0.7%) and the hindfoot in 4 of 583 (0.7%). In multivariate logistic regression analysis, initial hindfoot localization was a significant factor (P < .05), whereas peripheral artery disease, smoking, and a midfoot DFO were not found to be risk factors.Conclusion:In our retrospective series, the frequency of limb loss in DFO increased with more proximal initial foot DFO lesions, with almost half of patients losing their limbs with a hindfoot DFO.Level of Evidence:Level IV, retrospective cohort study.

Treatment Failures in Diabetic Foot Osteomyelitis Associated with Concomitant Charcot Arthropathy: The Role of Underlying Arteriopathy

ObjectiveTherapy for diabetic foot osteomyelitis (DFO) with Charcot neuroosteoarthropathy is challenging. In patients with diabetic Charcot osteomyelitis (DCO), both the anatomic deformity and infection must be addressed. This study assessed the outcomes of DCO therapy and variables associated with treatment failure and compared them with outcomes of DFO cases. MethodsA single-center, retrospective, case-control study was performed to compare 93 DCO episodes with 530 DFO episodes, using Kaplan-Meier survival curves and multivariate Cox regression analyses. ResultsClinical failure occurred in 21.5% of DCO compared with 22.3% in DFO episodes (p=0.89) and was associated with peripheral arterial disease (PAD) stages 3 or 4 (HR 6.1; CI 2.0-18.1) and chronic treatment with immunosuppressives (HR 7.4; CI 2.0-27.1). Major amputations were significantly more frequent in DCO (28% versus 13.6%; p<0.01) and associated with PAD stages 3 and 4 (HR 8.0; CI 2.2-29.4), smoking (HR 5.4; CI 1.2-24.6), alcohol abuse (HR 3.5; CI 1.1-10.6), and renal dialysis (HR 4.9; CI 1.3-18.9). ConclusionsClinical treatment failures did not differ between DCO and DFO. However, patients with DCO underwent major amputation twice as often as those with DFO. Unlike widespread belief, treatment failure in DCO patients may, similar to DFO, be associated with a striking epidemiological link to severe PAD.

Effect of Recombinant Human Parathyroid Hormone (1-84) on Resolution of Active Charcot Neuro-osteoarthropathy in Diabetes: A Randomized, Double-Blind, Placebo-Controlled Study

OBJECTIVEFractures in Charcot neuro-osteoarthropathy (CN) often fail to heal despite prolonged immobilization with below-knee casting. The aim of the study was to assess the efficacy of recombinant human parathyroid hormone (PTH) in reducing time to resolution of CN and healing of fractures.RESEARCH DESIGN AND METHODSPeople with diabetes and acute (active) Charcot foot were randomized (double-blind) to either full-length PTH (1-84) or placebo therapy, both in addition to below-knee casting and calcium and vitamin D3 supplementation. The primary outcome was resolution of CN, defined as a skin foot temperature difference >2°C at two consecutive monthly visits.RESULTSMedian time to resolution was 5 months (95% CI 4, 12) in intervention and 6 months (95% CI 2, 9) in control. There was no significant difference in time to resolution between the groups (mixed-effects logistic regression; P = 0.64). The hazard ratio of resolution was 0.84 (95% CI 0.41, 1.74; P = 0.64), and the odds ratio of resolution by 12 months was 1.22 (0.90, 1.67; P = 0.20) (intervention vs. control). On linear regression analysis, there were no significant differences in the effect of treatment on fracture scores quantitated on MRI scans (coefficient 0.13 [95% CI −0.62, 0.88]; P = 0.73) and on foot and ankle X-rays (coefficient 0.30 [95% CI −0.03, 0.63]; P = 0.07).CONCLUSIONSThis double-blind placebo-controlled trial did not reduce time to resolution or enhance fracture healing of CN. There was no added benefit of daily intervention with PTH (1-84) to below-knee casting in achieving earlier resolution of CN.