Background and purpose Charcot neuropathy is characterized by bone destruction in a foot leading to deformity, instability, and risk of amputation. Little is known about the pathogenic mechanisms. We hypothesized that the bone-regulating Wnt/β-catenin and RANKL/OPG pathways have a role in Charcot arthropathy.Patients and methods 24 consecutive Charcot patients were treated by off-loading, and monitored for 2 years by repeated foot radiography, MRI, and circulating levels of sclerostin, dickkopf-1, Wnt inhibitory factor-1, Wnt ligand-1, OPG, and RANKL. 20 neuropathic diabetic controls and 20 healthy controls served as the reference.Results Levels of sclerostin, Dkk-1 and Wnt-1, but not of Wif-1, were significantly lower in Charcot patients than in the diabetic controls at inclusion. Dkk-1 and Wnt-1 levels responded to off-loading by increasing. Sclerostin levels were significantly higher in the diabetic controls than in the other groups whereas Wif-1 levels were significantly higher in the healthy controls than in the other groups. OPG and RANKL levels were significantly higher in the Charcot patients than in the other groups at inclusion, but decreased to the levels in healthy controls at 2 years. OPG/RANKL ratio was balanced in all groups at inclusion, and it remained balanced in Charcot patients on repeated measurement throughout the study.Interpretation High plasma RANKL and OPG levels at diagnosis of Charcot suggest that there is high bone remodeling activity before gradually normalizing after off-loading treatment. The consistently balanced OPG/RANKL ratio in Charcot patients suggests that there is low-key net bone building activity by this pathway following diagnosis and treatment. Inter-group differences at diagnosis and changes in Wnt signaling following off-loading treatment were sufficiently large to be reflected by systemic levels, indicating that this pathway has a role in bone remodeling and bone repair activity in Charcot patients. This is of particular clinical relevance considering the recent emergence of promising drugs that target this system.

Objective-To investigate whether patients with severe radiographic osteoarthritis (OA) have a diVerent outcome at one year after total hip replacement than patients with moderate radiographic OA. To investigate sex related diVerences in preoperative radiographic and self reported status and in postoperative outcome. Methods-184 patients (96 women) with a mean age at surgery of 71.4 years (50-92), with primary OA of the hip were investigated preoperatively and six and 12 months postoperatively with two self administered questionnaires, SF-36 and WOMAC. The radiographs were evaluated by two independent radiologists using an atlas. Minimal joint space narrowing, osteophytes, cysts, sclerosis, and deformity were assessed. A summary grade 0-3 was made, based on joint space, where 3 is severe OA. The reference population for SF-36 consisted of 2901 subjects matched for age and sex from the general Swedish population. Results-162 patients fulfilled the study criteria. 113 had grade 3, 47 grade 2, and two grade 1 radiographic OA. There was no diVerence in preoperative or postoperative pain and physical impairment between patients with moderate and severe radiographic OA. There were no sex related diVerences in preoperative radiographic status, or in postoperative outcome. Neither were any diVerences in preoperative radiographic status of OA found in patients with previous total hip replacement of the contralateral hip, compared with those who had not been operated on before. All patients, regardless of preoperative radiographic OA stage, showed significant postoperative improvement and at one year achieved a health related quality of life similar to that of the reference group. Conclusion-The severity of radiographic changes indicating OA often weighs heavily in the surgeon's decision to perform a total hip replacement. Yet, the findings of this study emphasise that the preoperative radiographic stage of OA has no correlation with the postoperative outcome after one year. Furthermore, this study failed to detect any sex related diVerences in preoperative radiographic and self reported status or in postoperative outcome of hip replacement.

Our objective was to assess clubfoot anatomy by US in newborn babies before and in the early phase of treatment. Reproducible US projections and measurements were carried out on 30 untreated clubfeet in 22 children, consecutively included in the study. The position of the navicular in relation to the head of the talus was visualised in all feet. The mean distance between the medial malleolus and the navicular was significantly shorter in the clubfeet than in normal feet. There was a tendency to medial displacement of the cuboid. Soft tissue thickness at the medial side of the foot was increased in all deformed feet. The measurements showed an acceptable intra- and inter-observer reliability for the different variables assessed ( r=0.71-0.96, Pearson's correlation coefficient). With US it is possible to obtain well-defined planes of investigation that give important information about the clubfoot deformity concerning the talo-crural, the talo-navicular and the calcaneo-cuboid joints. The method is simple enough to be used in everyday clinical practice and we recommend it as a guide during the non-operative treatment and for preoperative planning.

BackgroundLittle is currently known of the pathophysiological mechanisms triggering Charcot arthropathy and regulating its recovery although foot trauma has been proposed as a major initiating factor by activation of proinflammatory cytokines leading to increased osteoclastogenic activity and progressive bone destruction. Several members of the IL-17 family of proinflammatory cytokines have been shown to play a key role in the pathogenesis of inflammatory conditions affecting bone and joints but none has previously been studied in Charcot foot patients. The aim of this study was to investigate the role of IL-17A, IL-17E and IL-17F in patients presenting with Charcot foot.MethodsTwenty-six consecutive Charcot patients were monitored during 2 years by repeated foot radiographs, MRI and circulating levels of IL-17A, IL-17E and IL-17F. Analysis of cytokines was done by ultra-sensitive chemiluminescence technique and data were analyzed by one-way repeated measures ANOVA. Neuropathic diabetic patients (n = 20) and healthy subjects (n = 20) served as controls.ResultsPlasma IL-17A and IL-17E in weight-bearing Charcot patients at diagnosis were at the level of diabetic controls, whereas IL-17F was significantly lower than diabetic controls. A significant increase in IL-17A and IL-17E reaching a peak 2–4 months after inclusion and start of offloading treatment in Charcot patients was followed by a gradual decrease to the level of diabetic controls at 2 years postinclusion. In contrast, IL-17F increased gradually from inclusion to a level not significantly different from diabetic controls after 2 years.ConclusionsCharcot patients display a significant elevation of all three IL-17 cytokines during the follow-up period relative values at diagnosis and values in control patients supporting a role in the bone repair and remodeling activity during the recovery phase. The rapid increase of IL-17A and IL-17E shortly after initiating off-loading treatment could suggest this to be a response to immobilization and stabilization of the diseased foot.

The aim of this study was to establish guidelines for US assessment of the talo-crural, the talo-navicular and the calcaneo-cuboid joints during the first year of life, which could serve as a reference while studying foot deformities. The feet of 54 healthy children were examined at birth and at the age of 4, 7 and 12 months by using three easily defined and reproducible US projections. With a medial projection the relation of the navicular in relation to the medial malleolus and the head of the talus was studied. A lateral projection revealed the calcaneo-cuboid relationship and a dorsal projection the talo-navicular alignment in the sagittal plane. Normal values for measurements of these cartilaginous relationships were established for the different age groups. Intra- and inter-observer reliability was assessed and found to be acceptable ( r=0.53-0.90, Pearson correlation coefficient). With US it is possible to obtain reproducible planes of investigation that give reliable information about the talo-crural, the talo-navicular and the calcaneo-cuboid relationships during the first year of life.