Patients living with type 1 diabetes mellitus (T1DM) can develop early onset osteoporosis and are exposed to an increased risk of fracture. Skeletal health can be influenced easily with diet and exercise. However, diabetes mellitus (DM)-related osteopathy is not emphasized in the public information campaigns on the American Diabetes Association, Diabetes UK, Diabetes Ireland or International Diabetes Federation websites. This investigation aims to assess the perceptions of patients regarding living with T1DM and their baseline knowledge on DM-related osteopathy. A survey was administered to 102 consenting individuals living with T1DM in attendance at the Galway University Hospital Diabetes Centre. Of the respondents, 44% were female and 56% male (mean age of 43). Respondents had T1DM for a mean of 21 years. Participants were asked to identify DM-related complications, including bone thinning and bone fractures. Respondents were primarily concerned about developing DM-related blindness, kidney damage and amputations, but not osteopathy. 49% of respondents did not identify osteopathy as a potential DM-related complication, 28% of respondents related DM with bone thinning and bone fractures, and 22% individuals only identified bone thinning or bone fractures. When asked for their primary source of DM-related information, endocrinologists and internet where identified. When comparable questions were asked of DM-related healthcare professionals, 56% did not recognize osteopathy as a complication of T1DM. This study demonstrated a low-level awareness of the impact living with T1DM has on bone health. The deployment of patient-interactive activities or educational modules may enhance the future health of individuals living with T1DM

Introduction. There are nearly 500,000 people with undiagnosed diabetes mellitus in the UK. The incidental finding vascular calcification on plain radiographs in patients with undiagnosed diabetes has the potential to alter patient management in those presenting with pathology. We hypothesised that the presence of vascular calcification on plain radiographs of the foot may predict the diagnosis of diabetes. The primary aim of this case control study was to determine the positive predictive value of vascular calcification to diagnose diabetes. Secondary aims were to determine the odds of having diabetes dependent on other known risk factors for calcification. Methods. A retrospective case control study of 130 diabetic patients were compared to 130 non-diabetic patients that were matched for age and gender. The presence of vascular calcification in anterior, posterior or plantar vessels, and length of calcification were measured on plain radiographs. McNemar's Chi-squared test and positive predictive values were calculated. Conditional logistic regression models were used to estimate the association between calcification and diabetes. Results. 28 patients had type I diabetes and 102 had type II diabetes. The mean age was 58.0 in both groups and 31.5% were females. 89.2% of those with diabetes had calcification present, and 23.1% in those without (p < 0.0001). Calcification in two vessels predicts diabetes with a positive predictive value of 91.2% (95% CI 82.1%–100%). The odds ratio for having diabetes is 78 (95% CI: 7.8 – 784) times higher in a person who has calcification in the blood vessels of their foot than in a person without calcification after adjusting for confounders. Conclusion. This study has demonstrated that vascular calcification in 2 vessels is over 90% predictive of a diagnosis of diabetes. This screening test could be used in future clinics when interpreting radiographs, aiding in the diagnosis of diabetes and altering patient management

Background. Ankle fractures associated with diabetes experience more complications following standard Open-Reduction-Internal-Fixation (ORIF) than those without diabetes. Augmented fixation strategies namely extended ORIF and hind-foot-nail (HFN) may offer better results, and early weightbearing in this group. The aim of this study was to define the population of patients with diabetes undergoing primary fixation for ankle fractures. Secondarily, to assess the utilisation of standard and augmented strategies and the effect of these choices on surgical outcomes including early post-operative weight bearing and surgical complications. Methods. A national-multicentre retrospective cohort study was conducted between January to June 2019 in 56 centres (10 Major- Trauma-Centres and 46 Trauma-Units) in the United Kingdom; 1360 specifically defined complex ankle-fractures were enrolled. Demographics, fixation choice, surgical and functional outcomes were recorded. Statistical analysis was performed to compare high-risk patients with/without diabetes. Results. There were 316 patients in the diabetes cohort with mean age 63.9yrs (vs. 49.3yrs in non-diabetes cohort), and greater frailty score >4 (24% vs.14% (non-diabetes cohort) (p<0.03); 7.5% had documented neuropathy. In the diabetes cohort, 79.7% underwent standard ORIF, 7.1% extended ORIF and 10.2% a HFN compared to 87.7%, 3.0% and 10.3% in the non-diabetes cohort. Surgical wound complications after standard-ORIF were higher in the diabetes cohort (15.1% vs. 8.7%) (p<0.02) but patients with diabetes who underwent augmented techniques showed little difference in surgical outcomes/complications to non-diabetes, even though early-weight- bearing rates were greater than standard-ORIF. Conclusion. Ankle fractures in diabetes occur in older, frailer patients; whilst lower than expected neuropathy rates suggest a need for improved assessment. Augmented surgical techniques may allow earlier weight-bearing without increasing complications in keeping with modern guidelines in ankle fracture management

Introduction. A common acute orthopaedic presentation is an ulcerated or infected foot secondary to diabetic neuropathy. Surgical debridement or amputation are often required to manage this complication of diabetes. International literature indicates that amputation may lead to further complications and an increased mortality rate. The aim of this study is to investigate the mortality rate associated with different surgical interventions. This will inform surgical management of patients presenting with acute foot complications from diabetes. Methods. This is a retrospective review of patients with diabetic foot infections aged >16 years attending Middlemore Hospital over a 10-year period (2012–2021). Clinical records were examined to determine whether patients were managed with no surgery, surgery but not amputation, or amputation. We recorded relevant baseline characteristics and comorbidities. Regression models were used to determine factors associated with mortality. Results. Over the study period, 1260 patients were included in analysis. Patients were divided into three groups, a control group who received no surgical intervention (n=554), those receiving surgery but not amputation (n=269), and those who underwent amputation (n=437). After adjustment for potential confounders, mortality rates were significantly higher in those who underwent amputation compared with those who received surgical intervention without amputation. Survival probability at 1 year and 5 years was highest in the surgical intervention but not amputation group. Conclusion. It is clinically important that there is a lower mortality rate in patients who undergo surgical intervention without amputation. Treatment that aims to salvage the limb rather than amputate should be considered in management of patients with diabetic foot complications to optimise their care

Introduction and Objective. Type 2 diabetes mellitus (T2DM), and the often concurrent obesity, causes metabolic changes that affect many organs and tissues, including bone. Despite a normal or even higher bone mineral density (BMD), T2DM has often been associated with a higher fracture risk, indicating a compromised bone quality. In this work, we use a novel congenic leptin receptor-deficient BioBreeding Diabetes Resistant rat (BBDR.cg.lepr.cp) to investigate the impact of T2DM and obesity on bone morphology and architecture at the microscale. Materials and Methods. Two different anatomical locations, i.e., femur and cranium, were studied combining micro-computed X-ray tomography (micro-CT) with scanning electron microscopy (SEM). Micro-CT data were examined using advanced image analysis tools in three-dimensions (3D). Results. Both parietal bones and femurs were smaller, i.e., thinner and shorter, respectively, in diabetic animals compared to healthy controls. Image analysis of the sagittal suture revealed a reduced suture width and length in diabetic animals, suggesting an altered bone apposition rate. Histomorphometry analysis from micro-CT data highlighted differences in microstructure of both trabecular and cortical femur between diabetic and healthy rats. In particular, bone volume fraction (BV/TV) was lower in the T2DM group, while trabecular spacing (Tb.Sp) was increased, overall indicating a higher porosity in diabetic trabecular bone. SEM revealed the presence of extended portions of hyper-mineralized cartilage in the distal femur of the diabetic animals. Conclusions. Micro-CT analyses, combined with SEM imaging, suggest that T2DM impacts bone growth and remodelling, in turn leading to differences in the structural organization at the microscale

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking. Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373–378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1

Abstract. Objectives. Diabetes has been associated with greater risk of complications and prolonged postoperative recovery following ankle trauma. Our cohort study seeks to review the operative management and outcomes of ankle fractures in diabetic adults relative to non-diabetic adults. Methods. Cases were identified using ICD-10 coding criteria. 572 patients from Jan 2016–2019 presented with ankle fractures; 34 in diabetic patients. Mechanism of injury and stability were determined from the index radiograph using a validated Lauge-Hansen classification algorithm. Admission, primary post-operative and discharge radiographs were reviewed independently by two foot and ankle reconstruction specialists to assess adequacy of fixation method. 32% of diabetic patients were managed non-operatively compared to 29% of the matched non-diabetic cohort. The distribution in Lauge-Hansen fracture pattern was comparable between cohorts. Non-diabetic controls were frequency age-matched 2:1. Results. Mean length of follow-up was significantly longer for diabetics (26 weeks) compared to non-diabetics (16 weeks). Post-operative wound complications (superficial wound infection, breakdown, dehiscence) occurred in 48% of the operated diabetic ankles, compared to 5% in non-diabetics (RR 8.1, 95% CI 2.5–26.4). Reoperation (RR 4.3, 95% CI 2.5–26.4, p=0.03) and non-wound complication rates (Charcot joint, mal/non-union, metalwork infection) were likewise significantly higher (RR 3.9, 95% CI 1.4–10.8, p=0.008) in diabetics. Amongst diabetics alone, those with an HbA1c >69 mmol/mol (n=14, 41%) demonstrated a significantly higher rate still of non-wound complications (RR 4.3, 95% CI 1.1–18., p=0.03) with a trend towards higher wound complication rates (RR 3, 95% CI 0.52–17, p=0.13). Conclusions. Poorly controlled diabetes is associated with substantially greater complication rates following ankle fracture than those with well controlled or normal blood sugar; high HbA1c > 69mmol/mol is a significant predictor of complicated follow-up. Locally we recommend management strategies that are influenced by the fracture pattern stability and the presence or absence of complicated or poorly managed diabetes. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Diabetes has been associated with greater risk of complications and prolonged postoperative recovery following ankle trauma. Our cohort study reviewed the operative management and outcomes of ankle fractures in diabetic adults relative to non-diabetic adults from Jan 2016–2019. Non-diabetic controls were frequency age-matched 2:1. 34 of 572 ankle fracture presentations were in diabetic patients, 32% managed non-operatively compared to 29% of the matched non-diabetic cohort. The distribution in Lauge-Hansen fracture pattern was comparable between cohorts. Mean length of follow-up was significantly longer for diabetics (26 weeks) compared to non-diabetics (16 weeks). Post-operative wound complications (superficial wound infection, breakdown, dehiscence) occurred in 48% of the operated diabetic ankles, compared to 5% in non-diabetics (RR 8.1, 95% CI 2.5–26.4). Reoperation (RR 4.3, 95% CI 2.5–26.4, p=0.03) and non-wound complication rates (Charcot joint, mal/non-union, metalware infection) were likewise significantly higher (RR 3.9, 95% CI 1.4–10.8, p=0.008) in diabetics. Amongst diabetics alone, those with an HbA1c >69 mmol/mol (n=14, 41%) demonstrated a significantly higher rate still of non-wound complications (RR 4.3, 95% CI 1.1–18., p=0.03) with a trend towards higher wound complication rates (RR 3, 95% CI 0.52–17, p=0.13). Poorly controlled diabetes is associated with substantially greater complication rates following ankle fracture than those with well controlled or normal blood sugar; high HbA1c > 69mmol/mol is a significant predictor of complicated follow-up. Locally we recommend management strategies that are influenced by the fracture pattern stability and the presence or absence of complicated or poorly managed diabetes

Aim. This retrospective case series reports the reoperation, major amputation, survival rates and mobility status in diabetic patients who underwent a trans-metatarsal amputation (TMA) managed within a multi-disciplinary diabetic foot care service. Methods and patients. Forty-one consecutive patients (37 men, 4 women) underwent a TMA between January 2008 to December 2017. They were retrospectively reviewed. The mean age at the time of surgery was 63 years (range 39 – 92). Results. Eighty-eight per cent (36/41) of the patients were followed-up. Four (11%) of the 36 patients required reoperation, including three major amputations (8%). All the patients requiring a reoperation were vasculopaths. The four-year patient survival rate following a TMA was 69% (25/36). Ninety-six per cent (21/22) of the surviving patients not requiring revision to a major amputation were fully mobile in bespoke orthoses, of whom a third required a stick. Conclusion. This study shows that transmetatarsal amputation in patients with diabetes, managed in a multi-disciplinary diabetic foot care service, is effective for limb salvage

Aims. To identify variables independently associated with same-day discharge (SDD) of patients following revision total knee arthroplasty (rTKA) and to develop machine learning algorithms to predict suitable candidates for outpatient rTKA. Methods. Data were obtained from the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) database from the years 2018 to 2020. Patients with elective, unilateral rTKA procedures and a total hospital length of stay between zero and four days were included. Demographic, preoperative, and intraoperative variables were analyzed. A multivariable logistic regression (MLR) model and various machine learning techniques were compared using area under the curve (AUC), calibration, and decision curve analysis. Important and significant variables were identified from the models. Results. Of the 5,600 patients included in this study, 342 (6.1%) underwent SDD. The random forest (RF) model performed the best overall, with an internally validated AUC of 0.810. The ten crucial factors favoring SDD in the RF model include operating time, anaesthesia type, age, BMI, American Society of Anesthesiologists grade, race, history of diabetes, rTKA type, sex, and smoking status. Eight of these variables were also found to be significant in the MLR model. Conclusion. The RF model displayed excellent accuracy and identified clinically important variables for determining candidates for SDD following rTKA. Machine learning techniques such as RF will allow clinicians to accurately risk-stratify their patients preoperatively, in order to optimize resources and improve patient outcomes. Cite this article: Bone Jt Open 2023;4(6):399–407

Aims. Several previously identified patient-, injury-, and treatment-related factors are associated with the development of nonunion in distal femur fractures. However, the predictive value of these factors is not well defined. We aimed to assess the predictive ability of previously identified risk factors in the development of nonunion leading to secondary surgery in distal femur fractures. Methods. We conducted a retrospective cohort study of adult patients with traumatic distal femur fracture treated with lateral locking plate between 2009 and 2018. The patients who underwent secondary surgery due to fracture healing problem or plate failure were considered having nonunion. Background knowledge of risk factors of distal femur fracture nonunion based on previous literature was used to form an initial set of variables. A logistic regression model was used with previously identified patient- and injury-related variables (age, sex, BMI, diabetes, smoking, periprosthetic fracture, open fracture, trauma energy, fracture zone length, fracture comminution, medial side comminution) in the first analysis and with treatment-related variables (different surgeon-controlled factors, e.g. plate length, screw placement, and proximal fixation) in the second analysis to predict the nonunion leading to secondary surgery in distal femur fractures. Results. We were able to include 299 fractures in 291 patients. Altogether, 31/299 fractures (10%) developed nonunion. In the first analysis, pseudo-R. 2. was 0.27 and area under the receiver operating characteristic curve (AUC) was 0.81. BMI was the most important variable in the prediction. In the second analysis, pseudo-R. 2. was 0.06 and AUC was 0.67. Plate length was the most important variable in the prediction. Conclusion. The model including patient- and injury-related factors had moderate fit and predictive ability in the prediction of distal femur fracture nonunion leading to secondary surgery. BMI was the most important variable in prediction of nonunion. Surgeon-controlled factors had a minor role in prediction of nonunion. Cite this article: Bone Jt Open 2023;4(8):584–593

Aims. Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. Methods. In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated. Results. A total of 52,286 patients were included, of whom 1,804 (3.5%) died. Hypertension, diabetes mellitus, and obesity, the most frequent comorbidities, were not associated with higher in-hospital mortality. Cardiac diseases as atrial fibrillation, cardiac pacemaker, or three-vessel coronary heart disease showed the highest risk for in-hospital mortality. Postoperative anaemia occurred in two-thirds of patients and showed an increased in-hospital mortality (OR 1.72; p < 0.001). Severe complications, such as organ failure, systemic inflammatory response syndrome (SIRS), or septic shock syndrome showed by far the highest association with in-hospital mortality (OR 39.20; 95% CI 33.07 to 46.46; p < 0.001). Conclusion. These findings highlight the menace coming from PJI. It can culminate in multi-organ failure, SIRS, or septic shock syndrome, along with very high rates of in-hospital mortality, thereby highlighting the vulnerability of these patients. Particular attention should be paid to patients with cardiac comorbidities such as atrial fibrillation or three-vessel coronary heart disease. Risk factors should be optimized preoperatively, anticoagulant therapy stopped and restarted on time, and sufficient patient blood management should be emphasized. Cite this article: Bone Jt Open 2024;5(4):367–373

Fragility fractures are skeletal complications associated with type 2 diabetes (T2D) causing disability, hospitalization, impaired quality of life, and increased mortality. Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk. We have recently shown that T2D affects the expression of genes controlling bone formation (SOST and RUNX2) and that accumulation of AGEs is associated with impaired bone formation in T2D. We hypothesized that Wnt/B- catenin target genes are down-regulated in bone of T2D subjects as a consequence of decreased SOST and AGEs accumulation. To this end, we studied gene expression in extracts of bone samples obtained from femoral heads of 14 subjects with relatively well-controlled T2D (HbA1c 6.5±1.7%) and 21 control, non-diabetic postmenopausal women (age >65 years) undergoing hip replacement. There were no differences in age (73.2± .8 vs. 75.2±8.5 years) or BMI (27.7±5.6 vs. 29.9±5.4 kg/m2) between control and T2D groups, respectively. Expression of LEF1 mRNA was significantly lower in T2D compared to non-diabetic subjects (p=0.002), while DKK1 was not different between groups (p=0.108). Correlation analysis showed that DKK1 (r2=0.038; p=0.043) and HbA1c (r2=0.503; p=0.048) increased with age in T2D. COL1A1 mRNA trended lower in T2D compared to controls (p=0.056). Bone volume (9,333 ± 1,443 vs. 15,53 ± 2,442 mm2; p=0.048), mineralized volume (9,278 ± 1,418 vs. 15,45 ± 2,444 mm. 2. ; p=0.048) and BV/TV (0,2125 ± 0,03114 vs. 0,3719 ± 0,03196 %; p=0.002) measured by bone histomorphometry were lower in T2D compared to controls. Our data show that even in patients with relatively good glycemic control, T2D decreases expression of Wnt/B-catenin target genes andCOL1A1, associated with decreased bone density. These results may help understand the mechanisms underlying bone fragility in T2D

Aims. The outcomes of patients with unexpected positive cultures (UPCs) during revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain unknown. The objectives of this study were to establish the prevalence and infection-free implant survival in UPCs during presumed aseptic single-stage revision THA and TKA at mid-term follow-up. Methods. This study included 297 patients undergoing presumed aseptic single-stage revision THA or TKA at a single treatment centre. All patients with at least three UPCs obtained during revision surgery were treated with minimum three months of oral antibiotics following revision surgery. The prevalence of UPCs and causative microorganisms, the recurrence of periprosthetic joint infections (PJIs), and the infection-free implant survival were established at minimum five years’ follow-up (5.1 to 12.3). Results. Of the 297 patients undergoing aseptic revisions, 37 (12.5%) had at least three UPCs obtained during surgery. The UPC cohort included 23 males (62.2%) and 14 females (37.8%), with a mean age of 71.2 years (47 to 82). Comorbidities included smoking (56.8%), hypertension (48.6%), diabetes mellitus (27.0%), and chronic renal impairment (13.5%). The causative microorganisms included Staphylococcus epidermidis (49.6%), Bacillus species (18.9%), Micrococcus species (16.2%), and Cutibacterium acnes (16.2%). None of the study patients with UPCs developed further PJIs or required further surgical intervention during follow-up. Conclusion. The prevalence of UPCs during presumed aseptic revision THA and TKA was 12.5%. The most common causative microorganisms were of low virulence, and included S. epidermidis, Bacillus species, Micrococcus species, and C. acnes. Microorganism-specific antibiotic treatment for minimum three months’ duration of UPCs in presumed aseptic revision arthroplasty was associated with excellent infection-free implant survival at mid-term follow-up. Cite this article: Bone Jt Open 2024;5(10):832–836

Introduction: As a consequence of the rising prevalence of diabetes worldwide, an increasing proportion of diabetic THR patients may be expected in coming years. Diabetes research on postoperative complications among arthroplasty patients is limited. We evaluated the extent to which diabetes affect the revision rate due to aseptic loosening, deep infection and dislocation following total hip arthroplasty (THA). Material and Methods: We used the Danish Hip Arthroplasty Registry (DHR) to identify all primary THR patients operated on during the period from 1 January 1996 to 31 December 2005. The presence of diabetes among THA patients was identified by using The Danish National Registry of Patients and The Danish National Drug Prescription Database. We used Poisson regression analyses, to estimate relative risk (RR) and 95% Confidence Interval (CI) for patients with diabetes compared to patients without diabetes, both crude and adjusted for potentially confounding factors. Results: We identified 57 575 first primary THR patients in DHR, of which 3 278 (5.7%) were with diabetes and 54 297 (94.3%) without diabetes. An adjusted RR for revision due to deep infection of 1.45 (CI: 1.00–2.09) was found for THA diabetic patients compared to patients without diabetes. The RR was particularly high for THA patients with diabetes less than five years (RR was 1.71 (CI: 1.24–32.34), with the presence of diabetes related comorbidites prior THA (RR was 2.35 (CI: 1.39–3.98) and diabetes related complications (RR was 1.88 (CI: 1.17–3.03). Conclusion. The patient and the surgeon should be aware of the relative increased risk of revision due to deep infection following THA as compared with the risk in THA patients without diabetes

Introduction. Tendon disease and rupture are common in patients with diabetes and these are exacerbated by poor healing. although nanoscale changes in diabetic tendon are linked to increased strength and stiffness. The resistance to mechanical damage of a tissue may be measured using fatigue testing but this has not been carried out in diabetic tendon, although the toughness of diabetic bone is known to be reduced. The aim of this study was to measure the static fatigue behaviour of tendons from a streptozotocin (STZ)-induced rat model of diabetes, hypothesising that diabetes causes tendon to show lower resistance to mechanical damage than healthy tendon. Materials and Methods. Diabetic (n=3, 12 weeks post-STZ) and age-matched control (n=3) adult male Sprague Dawley rats were culled, tails harvested and stored at −80ºC. Following defrosting, fascicles (5 per animal) were carefully dissected, mean diameter measured using an optical micrometer and mounted in a Bose Biodynamics test machine using custom grips in a PBS bath. Static fatigue testing at 30 MPa to failure enabled both elastic modulus (initial ramp) and steady state creep rate (gradient at creep curve inflexion) to be measured. Data are reported as median ± interquartile range and pw0.05 using a Mann-Whitney U test was taken as significant. Results. Confirming previous reports, tendon from diabetic rats showed significantly higher elastic modulus (201 ± 68 MPa) than healthy (151 ± 62 MPa). Strain at failure showed no differences between groups. Tendon from diabetic rats showed significantly slower steady state creep (71 ± 44 μstrain s. −1. ) than healthy (691 ± 1000 μstrain s. −1. ). Discussion. These preliminary data show an order of magnitude larger resistance to mechanical damage in diabetic tendons, possibly associated with the previously reported increased packing and decreased fibril diameters. Energy-storing flexor tendons, the most commonly affected in diabetics, and the positional tendons tested here show similar fatigue behaviour when tested at the same fraction of “stress-in-life”. Further investigation is required into the cell tissue repair response in diabetes in order to link reduced rates of mechanical damage with the clinically increased risk of disease and rupture in diabetic patients

Intervertebral disc degeneration (IDD) is a major cause of low back pain, which affects 80% of the adult population at least once in their life. The pathophysiological conditions underlying IDD are still poorly understood. Genetic makeup, aging, smoking, physical inactivity and mechanical overloading, especially due to obesity, are among the strongest risk factors involved. Moreover, IDD is often associated with chronic inflammation within disc tissues, which increases matrix breakdown, glycosaminoglycan (GAG) loss and cell death. This micro-inflammatory environment is typical of several metabolic disorders, including diabetes mellitus (DM). As the etiopathogenesis of IDD in diabetic subjects remains scarcely understood, we hypothesised that this may be driven by a DM-induced inflammation leading to a combination of reduced GAG levels, decreased proteoglycan synthesis and increased matrix breakdown within the disc. The objective of the study was to investigate the pathogenesis of IDD in a murine model of type 1 DM (T1DM), namely non-obese diabetic (NOD) mouse. Total disc glycosaminoglycan (GAG) content, proteoglycan synthesis, aggrecan fragmentation mediated by matrix metalloproteinases (MMPs) and a Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS), glucose transporter (mGLUT1) gene expression and apoptosis (TUNEL assay) were assessed in NOD mice and wild-type euglycemic control mice. Spinal structural and molecular changes were analysed by micro-computed tomography (mCT), histological staining (Safranin-O and fast green) and quantitative immunofluorescence (anti-ADAMTS-4 and 5 antibodies). Statistical analysis was conducted considering the average of 35 samples ± standard error for each measurement, with 95% confidence intervals calculated to determine statistical significance (p-value < 0.05). IVDs of NOD mice showed increased disc apoptosis (p < 0.05) and higher aggrecan fragmentation mediated by ADAMTS (p < 0.05). However, ADAMTS-4 and −5 did not appear to be involved in this process. The total GAG content normalized to DNA and PG synthesis showed no statistically significant alterations, as well as Safranin O staining. Although not significantly, NOD mice showed reduced glucose uptake. In addition, the vertebral structure of NOD mice at mCT seemed not to be altered. These data demonstrate that DM may contribute to IDD by increasing aggrecan degradation and promoting cell apoptosis, which may represent early indicators of the involvement of DM in the pathogenesis of IDD

Introduction: Diabetes mellitus type 2 (DM II) affects 18.2 million Americans and can cause several chronic and morbid complications. Furthermore, 90% of Americans have radiographic evidence of osteoarthritis by age 40. Diabetes may be an important risk factor for symptomatic osteoarthritis later in life. The aim of our study is to determine if diabetic patients are predisposed to osteoarthritis. Methods: We conducted a review of the all total knee arthroplasty (TKA) cases performed at our institute during the past two years for end stage osteoarthritis. We excluded TKAs performed for post-traumatic arthritis and patients with inflammatory diseases. Comorbidities and demographical information including age, gender, BMI, and family history were collected from our database. A cross sectional study was performed to analyze the prevalence of DM II in our population. This prevalence was compared to that of diabetics in the general population available from various sources including the National Center for Health Statistics. Results: Our cohort included a total of 3421 patients (1972 females, 1449 males) who had undergone TKA for end stage osteoarthritis. The average age and BMI were 66 years (range: 39–92) and 32 (range: 21–65) respectively. The prevalence of diabetes mellitus type 2 in our cohort was 12%, while the prevalence of DM II in the general US population currently ranges from 6%–7%. Discussion: Chronic diabetes causes multiorgan failure via microvascular and macrovascular damage and may possibly lead to degeneration of articular cartilage and eventual arthritis. Based on this study, diabetes appears to be a strong predisposing factor for arthritis. Our laboratory has launched an extensive series of experiments delinating the potential cellular mechanism for such association

Background. Patients with diabetes who sustain an ankle fracture are at increased risk for complications including higher rates of in-hospital mortality, in-hospital post-operative complications, length of stay and non-routine discharges. Aim. The purpose of this study was to retrospectively compare the complications associated with operatively treated ankle fractures in a group of patients with uncomplicated diabetes versus a group of patients with complicated diabetes. Complicated diabetes was defined as diabetes associated with end organ damage such as peripheral neuropathy, nephropathy and/or PAD. Uncomplicated diabetes was defined as diabetes without any of these associated conditions. Our hypothesis was that patients with uncomplicated diabetes would experience fewer complications than those patients with complicated diabetes. Methods. We compared the complication rates of ankle fracture repair in 46 patients with complicated diabetes and 59 patients with uncomplicated diabetes and calculated odds ratios (OR) for significant findings. At a mean follow up of 21.4 months we found that patients with complicated diabetes had 3.8 times increased risk of overall complications, 3.4 times increased risk of a non-infectious complication (malunion, nonunion or Charcot arthropathy) and 5 times higher likelihood of needing revision surgery/arthrodesis when compared to patients with uncomplicated diabetes. Open ankle fractures in this diabetic population were associated with a three times higher rate of complications and 3.7 times higher rate of infection. Conclusion. Patients with complicated diabetes have an increased risk of complications after ankle fracture surgery compared to patients with uncomplicated diabetes. Careful pre-operative evaluation of the neurovascular status is mandatory, since many patients with diabetes do not recognise that they have neuropathy and/or peripheral artery disease

Introduction. Knee arthroplasty provides not only pain relief but also an improvement in function and range of movement. Limited joint mobility (LJM), secondary to peri-articular connective tissues stiffness, is a common complication of diabetes mellitus. We therefore examined functional outcome post-total knee arthroplasty (TKA) in a cohort of subjects with and without diabetes mellitus. Method. The effect of TKA on indices of knee function (fixed flexion, maximum flexion, total ROM and knee society score) was examined in 367 subjects with type 2 diabetes and 367 subjects without diabetes. The groups were matched for age, sex, BMI and functional movement at baseline. Participants were examined at baseline (pre-operatively), 1, 5 and 10 years post-TKA. Results. There was no significant difference in fixed flexion, maximal flexion or total range of movement between the two groups at baseline. At 1 year the group with diabetes had a significantly lower maximal flexion (p < 0.001), total range of movement (p < 0.001) and Knee Society Score (p = 0.034). At 5 years post-arthroplasty a significant increase was observed in fixed flexion (p = 0.026) as well as a significant decrease in maximal flexion (p = 0.001) and total range of movement (p = 0.004) in the diabetic group. Ten years post-arthroplasty yielded similar results. Conclusion. Within one-year post-arthroplasty people with diabetes develop a poorer range of movement compared to controls. Between one to five years post-procedure a significant fixed flexion deformity occurred in those with diabetes. A sustained deterioration was observed up to 10 years post-procedure. This study is the first to demonstrate that the pre-operative presence of diabetes mellitus leads to a worse functional outcome post-knee arthroplasty