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

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

Objectives

Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model.

Background and aims:

T2D is postulated to be an important aetiological factor for lumbar disc degeneration (LDD), which itself has a well documented relationship with low back pain. Obesity increases risk of both T2D, low back pain and LDD. Connective tissue modification has been reported in hyperglycaemia, but the epidemiology of LDD in T2D has not been described to date.

Aims. Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results. Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion. These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666

The ability of the body to constantly maintain metabolism homeostasis while fulling the heightened energy and macromolecule demand is crucial to ensure successful tissue healing outcomes. Studies investigating the local metabolic environment during healing are scarce to date. Here, using Type 2 Diabetes (T2D) as a study model, we investigate the impact of metabolism dysregulation on scaffold-guided large-volume bone regeneration. Our study treated wild-type or T2D rats with 5 mm critical-sized femoral defects with 3D-printed polycaprolactone (PCL) scaffolds with 70% porosity. Metabolomics was leveraged for a holistic view of metabolism alteration as healing progress and correlated to regenerated bone tissue volume and quality assessed using micro-computed tomography (µ-CT), histology, and immunohistology. Semi-targeted metabolomics analysis indicated dysregulation in the glycolysis and TCA cycle – the main energy production pathways, in T2D compared to healthy animals. The abundance of metabolites substrates, i.e., amino acids – for protein/ extracellular matrix synthesis was also affected in T2D. Tissue-level metabolites observations aligned with morphological observation with less newly formed bone observed in T2D than wild-type rats. This study enlightens the metabolism landscape during scaffold-guided large-volume bone regeneration in wild-type vs. T2D to further guide the personalization of the scaffold to drive successful regeneration

There is growing interest in the peri-operative management of patients with indications for hip and knee arthroplasty in the setting of modifiable risk factors such as morbid obesity, type 2 diabetes mellitus, and smoking. A recent survey of the American Association of Hip and Knee Surgeons (AAHKS) found that 95% of respondents address modifiable risk factors prior to surgery. The aim of this study was to poll Australian arthroplasty surgeons regarding their approach to patients with modifiable risk factors. The survey tool used in the AAHKS study was adapted for use in the Australian context and distributed to the membership of the Arthroplasty Society of Australia via Survey Monkey. Seventy-seven survey responses were received, representing a response rate of 64%. The majority of respondents were experienced, high volume arthroplasty surgeons. Overall, 91% of respondents restricted access to arthroplasty for patients with modifiable risk factors. Seventy-two percent of surgeons restricted access for excessive body mass index, 85% for poor diabetic control, and 46% for smoking. Most respondents made decisions based on personal experience or literature review rather than hospital or departmental pressures. Despite differences in healthcare systems, our findings were similar to those of the AAHKS survey, although their responses were more restrictive in all domains. Differences were noted in responses concerning financial considerations for potentially underprivileged populations. The survey is currently being administered by arthroplasty societies in six other countries, allowing comparison of orthopaedic practice across different healthcare systems around the world. In conclusion, over 90% of Australian arthroplasty surgeons who responded to the survey address modifiable risk factors prior to surgery

Introduction. Diabetic foot disease is a major public health problem with an annual NHS expenditure in excess of £1 billion. Infection increases risk of major amputation fivefold. Due to the polymicrobial nature of diabetic foot infections, it is often difficult to isolate the correct organism with conventional culture techniques, to deliver appropriate narrow spectrum antibiotics. Rapid DNA-based technology using multi-channel arrays presents a quicker alternative and has previously been used effectively in intensive care and respiratory medicine. Methods. We gained institutional and Local Ethics Committee approval for a prospective cohort study of patients with clinically infected diabetic foot wounds. They all had deep tissue samples taken in clinic processed with conventional culture and real-time PCR TaqMan array. Results. 50 samples were taken from 39 patients between October 2020 and March 2022. 84% of patient were male, 88% had type 2 diabetes. The ulcers were of variable chronicity prior to sampling (range 1–113 weeks) and mean HbA1c was 67.2mmol/mol. Ulcers were on the heel (3), midfoot (6) and forefoot (41). Minimum follow up was 3 months. 6 ulcers healed, 24 patients were admitted due to foot disease, there were 2 major amputations and 4 deaths. TaqMan array results were available a mean of 4.3 days earlier than culture results. 9 patients had negative conventional cultures and 8 were negative onarray testing. 17 patients had the same organisms detected on culture and array. 16 of these 17 had additional organisms detected by array. The most frequent organisms detected on array that were not detected by culture were Staphylococcus spp., Enterobacter, Pseudomonas and fungi. Conclusion. TaqMan array shows promise in detecting infecting organisms from diabetic foot wounds and providing earlier results than standard culture, which may enable appropriate and timely antibiotic therapy

Introduction. Charcot neuroarthropathy is a debilitating condition that frequently leads to skeletal instability, and has an increased risk of ulceration leading to infection and amputation. However, surgical reconstruction may offer limb salvage and restauration of an ulcer-free, plantigrade stable foot for functional weight-bearing. We report on our case series according to a prospective protocol and analyse factors leading to a favourable outcome. Methods. We report a prospective follow-up of 62 patients undergoing Charcot reconstruction, May 2014- Jan 2022, by two surgeons. Peripheral vascular disease was routinely assessed using Duplex scan and major arterial disease was treated before reconstruction. Utilising 3D modelling, pre-operative planning and standardised osteotomies, we performed anatomical correction with radiological evidence. Definitive fixation was undertaken with internal fixation to stabilise the hindfoot. Multivariant analysis was performed to assess risk factors for failure (P>0.05 statistical significance). Results. 59 feet were included, 3 patients did not progress to definitive surgery and 3 patients had bilateral surgery. 62.7% patients were male with an average age of 56, 88.13% had Type 2 diabetes, 56% were hypertensive, 14% were on dialysis. Twenty (54.1%) single stage reconstructions had pre-operative ulceration, 3 pts had ischaemic heart disease and 36 pts had evidence of peripheral arterial disease. 81% of patients achieved normalisation of the 3 out of 4 anatomical angles (P<0.05). Two patients (3.1%) required metalwork removal for infection and limb salvage, 11 (18.6%) had delayed wound healing. Survivorship was 97% at 3yrs, and 94% at 6yrs, however if pre-existing vascular disease was present, it was 94% at 3yrs 85.3% at 6yrs. All patients were mobile at a 3 years mean follow up. Conclusion. Careful patient selection, multidisciplinary team and anatomic reconstruction led to predictable outcomes and functional limb salvage. Pre-operative vascular compromise led to a slight reduction in survivorship, but no major amputation

Abstract. Objectives. The aim of this study was to investigate whether mechanical loading induced by physical activity can reduce risk of sarcopenia in middle-aged adults. Methods. This was a longitudinal study based on a subset of UK Biobank data consisting of 1,918 participants (902 men and 1,016 women, mean age 56 years) who had no sarcopenia at baseline (assessed between 2006 and 2010). The participants were assessed again after 6 years at follow-up, and were categorized into no sarcopenia, probable sarcopenia, or sarcopenia according to the definition and algorithm developed in 2018 by European Working Group on Sarcopenia in Older People (EWGSOP). Physical activity was assessed at a time between baseline and follow-up using 7-day acceleration data obtained from wrist worn accelerometers. Raw acceleration data were then analysed to study the mechanical loading of physical activity at different intensities (i.e. very light, light, moderate-to-vigorous). Multinominal logistic regression was employed to examine the association between the incidence of sarcopenia and physical activity loading, between baseline and follow up, controlled for other factors at baseline including age, gender, BMI, smoking status, intake of alcohol, vitamin D and calcium, history of rheumatoid arthritis, osteoarthritis, secondary osteoporosis, and type 2 diabetes. Results. Among the 1918 participants with no sarcopenia at baseline, 230 (69 men and 161 women) developed probable sarcopenia and 37 (14 men and 23 women) developed sarcopenia at follow-up. Physical activity loading at moderate-to-vigorous intensity was higher in men (p<0.05), while women had higher physical activity loading at very light intensity (p<0.05). No significant difference was found in physical activity loading at light intensity between men and women (p>0.05). Logistic regression models showed that increase in physical activity loading at moderate-to-vigorous intensity significantly reduced the risk of sarcopenia (odds ratio = 0.368, p<0.05), but not probable sarcopenia (odds ratio = 0.974, p>0.05), while loading at light or very light activity intensity were not associated with the risk of sarcopenia or probable sarcopenia (p>0.05). Conclusion. Loading of physical activity at moderate-to-vigorous intensity could reduce risk of sarcopenia in middle-aged adults. 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

Osteoarthritis (OA) is the most prevalent degenerative joint disease that is a leading cause of disability worldwide. Existing therapies of OA only address the symptoms. Liraglutide is a well-known anti-diabetic medication that is used to treat type 2 diabetes and obesity. In inflammatory and post-traumatic OA animal models, liraglutide has demonstrated anti-inflammatory, pain-relieving, and cartilage-regenerating effects1 . The objective of this study is to investigate liraglutide's ability to reduce inflammation and promote anabolism in human OA chondrocytes in vitro. Pellets formed with human OA chondrocytes were cultured with a chondrogenic medium for one week to form cartilage tissue. Afterward, pellets were cultured for another 2 weeks with a chondropermissive medium. The OA group was treated with IL-1β to mimic an inflammatory OA condition. The drug group was treated with 0.5 or 10 µM liraglutide. On days 0, 1, and 14, pellets were collected. Conditioned medium was collected over the 2 weeks culture period. The gene and protein expression levels of regenerative and inflammatory biomarkers were evaluated and histological analyzes were performed. Results showed that the nitric oxide release of the OA + 0.5 µM liraglutide and OA + 10 µM liraglutide groups were lower than the OA group. The DNA content of the OA + 0.5 µM liraglutide and OA + 10 µM liraglutide groups were higher than the OA group on day 14. The RT-qPCR results showed that the anabolism (ACAN, COMP, and COL2) markers were higher expressed in the OA + 0.5 µM liraglutide and OA + 10 µM liraglutide groups when compared with the OA group. The inflammation (CCL-2 and IL-8) markers and catabolism markers (MMP-1, MMP-3, ADAMTS4, and ADAMTS5) had lower expression levels in the OA + liraglutide groups compared to the OA group. The histomorphometric analysis (Figure 1) supported the RT-qPCR results. The results indicate that liraglutide has anabolic and anti-inflammatory effects on human OA chondrocyte pellets. Acknowledgments: This project has received funding from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and innovation program. The funding agencies supporting this work are (in alphabetical order of participating countries): France: BPI France; Germany: Project Management Agency (DLR), which acts on behalf of the Federal Ministry of Education and Research (BMBF); The Netherlands: Netherlands Enterprise Agency (RVO); Switzerland: Innosuisse (the Swiss Innovation Agency). For any figures and tables, please contact the authors directly

Aims. Type 2 diabetes mellitus (T2DM) impairs bone strength and is a significant risk factor for hip fracture, yet currently there is no reliable tool to assess this risk. Most risk stratification methods rely on bone mineral density, which is not impaired by diabetes, rendering current tests ineffective. CT-based finite element analysis (CTFEA) calculates the mechanical response of bone to load and uses the yield strain, which is reduced in T2DM patients, to measure bone strength. The purpose of this feasibility study was to examine whether CTFEA could be used to assess the hip fracture risk for T2DM patients. Methods. A retrospective cohort study was undertaken using autonomous CTFEA performed on existing abdominal or pelvic CT data comparing two groups of T2DM patients: a study group of 27 patients who had sustained a hip fracture within the year following the CT scan and a control group of 24 patients who did not have a hip fracture within one year. The main outcome of the CTFEA is a novel measure of hip bone strength termed the Hip Strength Score (HSS). Results. The HSS was significantly lower in the study group (1.76 (SD 0.46)) than in the control group (2.31 (SD 0.74); p = 0.002). A multivariate model showed the odds of having a hip fracture were 17 times greater in patients who had an HSS ≤ 2.2. The CTFEA has a sensitivity of 89%, a specificity of 76%, and an area under the curve of 0.90. Conclusion. This preliminary study demonstrates the feasibility of using a CTFEA-based bone strength parameter to assess hip fracture risk in a population of T2DM patients. Cite this article: Bone Joint J 2021;103-B(9):1497–1504

The increased incidence of type 2 Diabetes Mellitus is associated with an impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin is a negative regulator of bone formation produced by osteocytes and there is recent evidence that its expression in serum is elevated in diabetic patients compared to control subjects. In this study, we test whether hyperglycemia affects serum and bone sclerostin levels in a rat model of type 2 Diabetes as well as sclerostin production by osteoblasts in culture. We used Zucker diabetic fatty (ZDF) male rats (n=6) that spontaneously develop obesity and frank diabetes around 8–9 weeks of age and Zucker lean rats as controls (n=6) to examine sclerostin expression in serum at 9, 11 and 13 weeks using a specific ELISA. Sclerostin expression in bone tibiae was examined at 12 weeks using immunocytochemistry. Rat osteoblast-like cells UMR-106 were cultured in the presence of increasing concentrations of glucose (5, 11, 22 and 44 mM) during 48 hours and sclerostin mRNA expression and release in the supernatant determined by quantitative PCR and ELISA, respectively. Our results show that serum sclerostin levels are higher in the diabetic rats compared to lean rats at 9 weeks (+ 140%, p<0.01). Our preliminary results using immunocytochemistry for sclerostin did not show any major difference in sclerostin expression in tibiae of diabetic rats compared to lean ones, although we observed many osteocytic empty lacunae in cortical bone from diabetic rats. Glucose dose-dependent stimulated sclerostin mRNA and protein production in mature UMR106 cells while it had no effect on osteocalcin expression. Altogether, our data suggest that sclerostin production by mature osteoblasts is increased by hyperglycemia in vitro and enhanced in serum of diabetic rats. Furthers studies are required to determine whether sclerostin could contribute to the deleterious effect of Diabetes on bone

Introduction and Objective. Individuals with type 2 diabetes (T2D) have a 3-fold increased risk of bone fracture compared to non-diabetics, with the majority of fractures occurring in the hip, vertebrae and wrists. However, unlike osteoporosis, in T2D, increased bone fragility is generally not accompanied by a reduction in bone mineral density (BMD). This implies that T2D is explained by poorer bone quality, whereby the intrinsic properties of the bone tissue itself are impaired, rather than bone mass. Yet, the mechanics remain unclear. The objective of this study is to (1) assess the fracture mechanics of bone at the structural and tissue level; and (2) investigate for changes in the composition of bone tissue along with measuring total fluorescent advanced glycation end products (fAGEs) from the skin, as T2D progresses with age in Zucker diabetic fatty (ZDF (fa/fa)) and lean Zucker (ZL (fa/+)) rats. Materials and Methods. Right ulnae and skin sections were harvested from ZDF (fa/fa) (T2D) and ZL (fa/+) (Control) rats at 12 and 46 weeks (wks) of age (n = 8, per strain and age) and frozen. Right ulnae were thawed for 12 hrs before micro-CT (μCT) scanning to assess the microstructure and measure BMD. After scanning, ulnae were loaded until failure via three-point bending. Fourier transform-infrared microspectroscopy (FTIR) was used to measure various bone mineral- and collagen-related parameters such as, mineral-to-matrix ratio and nonenzymatic cross-link ratio. Finally, fAGEs were measured from skin sections using fluorescence spectrometry and an absorbance assay, reported in units of ng quinine/ mg collagen. Results. At 12 and 46 wks bone size was significantly smaller in length (p < 0.01), cortical area (p < 0.001) and cross-sectional moment of inertia (p < 0.001) in T2D rats compared to age-matched controls. A slight reduction in BMD was observed in T2D rats compared to controls at both ages, however, this was not significant. Structural properties of T2D bone were significantly altered at 12 and 46 wks, with bending rigidity increasing approximately 2.5-fold and 1.5-fold in control and T2D rats with age, respectively (p < 0.0001). Similarly, yield and ultimate moment significantly reduced in T2D rats with age in comparison to controls (p < 0.0001). Energy absorbed to failure was significantly reduced in T2D rats at 46 weeks of age compared to controls (p < 0.01). The amount of energy absorbed to failure increased approximately 1.4-fold from 12 to 46 wks in control rats, however, in T2D rats a reduction was seen with age, although not significant. At 12 wks, there was no significant deficits in tissue material properties, whereas, at 46 wks a significant reduction in yield stress, yield strain and ultimate stress was observed for T2D rats in comparison to controls (p < 0.05). Conclusions. These findings show that longitudinal growth is impaired as early as 12 wks of age and by 46 wks bone size is significantly reduced in T2D rats compared to controls. The reduction in T2D structural properties is likely attributed to the bone geometry deficits. At 12 wks of age, the tissue material properties are not altered in T2D bone versus controls. However, at 46 wks, bone strength is reduced in T2D, leading to the conclusion that tissue properties are altered as the disease progresses

We have evaluated the extent to which diabetes affects the revision rate following total hip replacement (THR). Through the Danish Hip Arthroplasty Registry we identified all patients undergoing a primary THR (n = 57 575) between 1 January 1996 and 31 December 2005, of whom 3278 had diabetes. The presence of diabetes among these patients was identified through the Danish National Registry of Patients and the Danish National Drug Prescription Database. We estimated the relative risk for revision and the 95% confidence intervals for patients with diabetes compared to those without, adjusting for the confounding factors. Diabetes is associated with an increased risk of revision due to deep infection (relative risk = 1.45 (95% confidence interval 1.00 to 2.09), particularly in those with type 2 diabetes (relative risk = 1.49 (95% confidence interval 1.02 to 2.18)), those with diabetes for less than five years prior to THR (relative risk = 1.69 (95% confidence interval 1.24 to 2.32)), those with complications due to diabetes (relative risk = 2.11 (95% confidence interval 1.41 to 3.17)), and those with cardiovascular comorbidities prior to surgery (relative risk = 2.35 (95% confidence interval 1.39 to 3.98)). Patients and surgeons should be aware of the relatively elevated risk of revision due to deep infection following THR in diabetes particularly in those with insufficient control of their glucose level

Introduction. Corrective fusion for the unstable deformed hind foot in Charcot Neuroarthropathy (CN) is quite challenging and is best done in tertiary centres under the supervision of multidisciplinary teams. Patients and methods. We present our results with a series of 42 hind foot deformity corrections in 40 patients from a tertiary level teaching hospital in the United Kingdom. The mean patient age was 59 (33–82). 16 patients had type1 diabetes mellitus, 20 had type 2 diabetes and 4 were non-diabetic. 18 patients had chronic ulceration. 17 patients were ASA 2 and 23 were ASA grade 3. All patients had acute single stage correction and Trigen hind foot nail fusion performed through a standard technique by the senior author and managed peri-operatively by the multidisciplinary team. Our outcome measures were limb salvage, deformity correction, ulcer healing, weight bearing in surgical shoes and return to activities of daily living (ADL). Results. At a mean follow up of 37 months (7–79) we achieved 100% limb salvage initially and 97% healing of arthrodesis. One patient with persisting non-union has been offered amputation. Deformity correction was achieved in 100% and ulcer healing in 89%. 72.5% patients are able to mobilize and manage independent ADL. There were 11 patients with one or more complications including metal failure, infection and ulcer reactivation. We performed nine repeat procedures including one revision fusion and one vascular procedure. Conclusion. Single stage corrective fusion for hind foot deformity in CN is an effective procedure when delivered by a skilled multidisciplinary team

In developed nations Charcot arthropathy is most commonly caused by diabetes mellitus. Worldwide, leprosy remains the primary cause. All evidence points to a relationship between neurologic loss, continued loading activities and the development of unrecognized bone fragmentation. In type 2 diabetes, dysregulation of leptin biology causes bone loss and may be an important factor in precipitating Charcot events. Bone density studies show massive loss of bone in patients with ankle and hindfoot Charcot problems, but not midfoot problems. This suggests a different mechanism for collapse. Stable collapse with ulcer development in the midfoot can be treated with exostectomy. Realignment and fusion remain the mainstays of treatment for diabetic Charcot neuropathy, especially in the ankle and hindfoot. Bone mineralization deficiencies require special consideration of fixation techniques. Thin wire external fixation – either as primary fixation or to reinforce/neutralize other methods can be very helpful. Large bridging screws and carefully selected bridging plates are frequently also valuable to consider. Excessive immobilization periods (often double the normal amount of time) are generally required. The goal may be limited to a braceable, plantigrade foot

Clinical evidence that patients with type 2 diabetes mellitus (T2DM) have increased risk of fractures is reported. Furthermore, thiazolidinediones, used to treat T2DM increases the risk of secondary osteoporosis & subsequent fractures. The osteogenic potency of metformin is reported in vitro, few studies have investigated the effects of metformin on bone mass and fracture healing in vivo. We aimed to investigate the effects of metformin on fracture healing in vivo. Method. 20 female Wistar rats aged 3 months were randomly divided in two groups, one group receiving saline, the other group receiving metformin administered orally via the drinking water at a concentration of 2mg/ml. After 4 weeks of metformin treatment, a mid-diaphyseal, open External fixation fracture was performed. Rats were sacrified 4 weeks later. Right contralateral tibia and left osteotomised femora were excised, bone architecture analysed by micro-CT in the right tibia. Results. No significant differences were noted between the two groups. Fracture callus volume and mineral content after 4 weeks were similar in metformin and saline groups. Discussion Our results indicate that while metformin has no adverse effects on bone, it does not promote bone mass, as suggested by in vitro studies. This confirms clinical data which have not shown direct links between metformin and decreased fracture risk

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

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Context: Diabetes is associated with a several fold increase in the risk of lower extremity amputation. Although a number of epidemiologic studies have reported positive associations between glycaemia and lower extremity amputation, the magnitude of the risk has not been adequately quantified. Objective: To synthesize the available prospective epidemiologic data on the association between glycaemia as measured by glycosylated haemoglobin and lower extremity amputation in individuals with diabetes. Data Sources: We searched electronic databases (MED-LINE and EMBASE) and the reference lists of relevant articles. Study Selection: We considered prospective epidemiologic studies of cohort or nested case-control design that measured glycosylated haemoglobin level and assessed lower extremity amputation as an outcome. Of 2,398 citations identified, we included 14 studies comprising 94,640 subjects and 1,227 cases. Data Extraction: Data were abstracted using standardized forms or obtained from investigators when published information was insufficient. Data included characteristics of case and control populations, measurement of glycaemia, assay methods, outcome, and covariates. Results: The overall risk ratio for lower extremity amputation was 1.26 (95% CI, 1.16–1.36) for each percentage point increase in glycosylated hemoglobin level. There was significant heterogeneity across studies (I2: 76%, 67–86%; p< 0.001) not accounted for by recorded study characteristics. Among studies that reported the type of diabetic population, the combined estimate was 1.44 (1.25–1.65) for individuals with type 2 diabetes and 1.18 (95% CI, 1.02–1.38) for type 1 diabetes, but the difference was not statistically significant (p=0.09). We found no significant publication bias. Conclusions: There a substantial increase in risk of lower extremity amputation associated with every 1% higher HbA1c in individuals with diabetes, highlighting a potential benefit of blood glucose control. In the absence of evidence from clinical trials, this paper supports glucose-lowering as a component of overall care in the patient at high risk of amputation

Introduction: Diabetes mellitus is a systemic disease affecting peripheral nerves and the use of regional anaesthesia in diabetic patients undergoing surgery could be unpredictable. We investigated the efficacy of brachial plexus block in diabetic patients undergoing upper limb surgery compared to normal individuals. Method: Four hundred and fifty-two patients had a brachial plexus block performed under ultra-sound guidance by senior anaesthetists. There were 221 males and 231 females. Fifty-five patients were diabetic (mean age of 61 years, SD 12), 24 with type 1 and 31 with type 2 diabetes. Mean age of non-diabetic patients was 55 years (SD 15). A mixture of 0.5% Bupivacaine and 1% Prilocaine was used for the block. Post-operative proximal and distal motor and sensory functions were assessed. The assessment was conducted at a mean of 4.6 hours (SD 2.2 hours) post-operatively. MRC grading system was used to asses motor function while sensory function was assessed subjectively using a graded scale between 0, absent sensation, 1, altered sensation and 2, normal sensation. Results: Brachial plexus block was as efficient in diabetic patients proximally for motor and sensory functions compared to non-diabetic patients. There was significant difference in the efficacy of the block distally between diabetic and non-diabetic patients in both motor (P< 001) and sensory function (P< 0001). Furthermore, in diabetic patients the response to the block between type 1 and type 2 was statistically significant (P< 001). Conclusion: In diabetes, the efficacy of brachial plexus block is different compared to normal individuals. This study showed that brachial plexus block can be used efficiently in shoulder surgery in patients with diabetes. In more distal surgery, orthopaedic surgeons as well as anaesthetists should be prepared to either reinforce the block by using a local anaesthetic or to convert to general anaesthesia, if necessary, in diabetic patients

Aims. Hip fractures pose a significant burden on the healthcare system. Hyperglycaemia and a state of Type 2 diabetes exists post operatively. Being normoglycaemic has well documented benefits. Pre operative carbohydrate loading has been shown to have two good effects. It decrease hyperglycaemia post operatively and allows the patient to undergo less strict fasting protocols. Insulin resistance to date has not been examined in these patients and this was determined using a validated formula (HOMA/IR). Methods. Three trauma hospitals were enrolled and patients with hip fractures requiring operative fixation were enlisted. Exclusion criteria: diabetic patients and inability to imbibe. 100 neck of femur fractures were examined. 46 patients were fasted normally. 32 test patients were given a carbohydrate rich drink pre operatively the night before surgery and in the morning up to 2 hours prior to surgery. 22 patients were excluded. Serum random glucose and insulin levels were taken on admission. Fasting serum glucose and insulin levels were taken on day one post operatively. Results. Control vs Trial average age: 82y and 75y. Admission glucose levels for Control vs Pre Op Loading: 6.5 vs 6.77 mmol/l. The average post operative Control vs Pre Op Loading: Glucose: 7.59 mmol/l vs 6.23mmol/. HOMA/IR in the control vs Pre Op loading group were: 1.86 and 1.2 compared to Post Op readings of 12 and 2. Paired T Test shows that there is significant decrease in hyperglycaemia and insulin resistance (p< 0.05). Conclusions. Pre operative carbohydrate loading leads to a decrease in hyperglycaemia and insulin resistance after surgery for hip fractures. Furthermore, patients are permitted a more liberal fasting regime leading to improved patient well being and less anxiety. The morbidity associated with a hyperglycaemic diabetic state is well documented and avoidance of this may lead to a decreased burden on the healthcare system

Introduction: Diabetes mellitus is a systemic disease that is known to affect peripheral nerves. The use of regional anaesthesia in diabetic patients undergoing surgery could be unpredictable. We investigated the efficacy of brachial plexus block in diabetic patients undergoing upper limb surgery compared to normal individuals. Methods: Four hundred and fifty-two patients were included in the study. There were 221 males and 231 females. Fifty-five patients were diabetic (mean age of 61ys, SD 12), 24 were type 1 and 31 were type 2 diabetes. Mean age of non-diabetic patients was 55 (SD15). Senior Anaesthetists performed all brachial plexus block under ultra-sound guidance. A mixture of 10 ml of 0.5% Bupivacaine and 10 ml of 1% Xilocaine was used for the block. Post-operative motor and sensory function assessment was conducted at a mean time of 4.57 hours (SD 2.19 hours). MRC grading system was used to asses motor function while sensory function was assessed subjectively using a graded scale between 0 and 2 with 0 being absent sensation, 1 being altered sensation and 2 indicated normal sensations. The assessment was conducted proximally and distally. Results: Brachial plexus block was as efficient in diabetic patients proximally for motor and sensory functions compared to non-diabetic patients. There was significant difference in the efficacy of the block distally between diabetic and non-diabetic patients in both motor (P< .001) and sensory function (P< .001). Furthermore, in diabetic patients the response to the block between type 1 and type 2 was statistically significant (P< .001). Conclusion: Diabetic patients are at increased morbidity and mortality risks following general anaesthesia and therefore, regional block is a favorable option in these patients. In diabetes, the efficacy of brachial plexus block is different compare to normal individuals. This study showed that brachial plexus block can be used efficiently in shoulder surgery in patients with diabetes. In more distal surgery, orthopaedic surgeons as well as anaesthetists should be prepared to either reinforce the block by using a local anaesthetic or to convert to general anaesthesia, if necessary, in diabetic patients

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Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

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Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined.

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Traumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in motor impairment affecting the upper limbs more than the lower, with occasional sensory impairment and urinary retention. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study was to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age.

Our aim was to determine the prevalence of shoulder symptoms in patients with type I compared to type 2 diabetes mellitus and evaluate the clinical presentation of patients diagnosed with adhesive capsulitis. This was a retrospective case-note review of 164 diabetic patients treated for shoulder symptoms from 1996 to 2007. Diabeta 3 for relevant Diabetic data. We used ANOVA, Tukey HSD, Chi-Square and Fisher’s Exact tests. The incidence of treated shoulder patients in diabetic population: 1.04%. 86 males; 78 females. Average age 58 years (22 – 83). DM Type I 34% (46/136); Type II 66% (90/136). Mean duration of DM at presentation: 10 years (1–33). Mean HbA1c at presentation 8.3%. Retinopathy 16% (19/90); Neuropathy 12% (12/88). The diagnoses were: Impingement 101 (62%); Adhesive Capsulitis 35 (21%); Cuff tear 17 (10%); Arthritis 11 (7%). Mean recorded pre-treatment ROM: Impingement (flexion 117°, abduction 103°, ER 36°); Adhesive Capsulitis (flexion 90°, abduction 75°, ER 12°); Cuff tear (flexion 109°, abduction 95°, ER 45°); Arthritis (flexion 67°, abduction 93°, ER 18°). Adhesive Capsulitis was significantly related to: HbA1c (9.9%); p< 0.001, Type I DM; p< 0.003, Duration of DM (average 17.5 yrs); p< 0.03. An interesting statistically significant (p< 0.003) correlation was found between Type 2 DM and Impingement Syndrome. Treatments included: Injection (53), MUA (49), Arthroscopy (99), Open Surgery (56). 82% patients satisfactorily discharged (mild/no pain and improved ROM: flexion > 150°, abduction > 150° and ER > 50°) after an average 3.4 months. Three referred to pain clinic, sixteen patients didn’t attend their follow-up appointment and seven died. Eleven relapsed (eight adhesive capsulitis). Persistent symptoms were more common in Diabetic patients with adhesive capsulitis, which was found to be significantly related to Type I DM, its duration and control (HbA1c levels). Type II Diabetics are more likely to be affected with impingement syndrome. Close liaison with the Diabetology Department is essential for effective treatment of Diabetic Shoulder pathology

The June 2024 Research Roundup³⁶⁰ looks at: Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels?; Large-scale assessment of ChatGPT in benign and malignant bone tumours imaging report diagnosis and its potential for clinical applications; Long-term effects of diffuse idiopathic skeletal hyperostosis on physical function: a longitudinal analysis; Effect of intramuscular fat in the thigh muscles on muscle architecture and physical performance in the middle-aged females with knee osteoarthritis; Preoperative package of care for osteoarthritis an opportunity not to be missed?; Superiority of kinematic alignment over mechanical alignment in total knee arthroplasty during medium- to long-term follow-up: a meta-analysis and trial sequential analysis.

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Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear.

The December 2023 Foot & Ankle Roundup³⁶⁰ looks at: Subchondral bone cysts remodel after correction of varus deformity in ankle arthritis; 3D-printed modular endoprosthesis reconstruction following total calcanectomy; Percutaneous partial bone excision in the management of diabetic toe osteomyelitis; Hemiepiphysiodesis is a viable surgical option for Juvenile hallux valgus; Ankle arthroplasty vs arthrodesis: which comes out on top?; Patient-related risk factors for poorer outcome following total ankle arthroplasty; The Outcomes in Ankle Replacement Study.

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Dupuytren’s contracture is characterized by increased fibrosis of the palmar aponeurosis, with eventual replacement of the surrounding fatty tissue with palmar fascial fibromatosis. We hypothesized that adipocytokines produced by adipose tissue in contact with the palmar aponeurosis might promote fibrosis of the palmar aponeurosis.

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The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI).

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Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

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Surgical reconstruction of deformed Charcot feet carries a high risk of nonunion, metalwork failure, and deformity recurrence. The primary aim of this study was to identify the factors contributing to these complications following hindfoot Charcot reconstructions.

Purpose: Since 1996, our multidisciplinary medicosurgical team has decided to propose orthopaedic treatment for diabetic perforating ulcers with osteitis, cellulitis, or necrosis (“cooling down” the acute infected ulcers before programmed surgery) rather than conservative treatment with prolonged antibiotic therapy. We present here a prospective study of 44 cases of diabetic perforating ulcers. Material and methods: Thirty-two diabetic patients underwent surgery: 77% males, mean age 65.2±8.6 year (range 43–86 years), 87% type 2 diabetes, 52% with a history of perforating ulcers, 45% with minor amputations, and 14% with history of vascular surgery. The lesions—perforating ulcer with osteitis (n=34), vascular necrosis of the toes (n=2), “acute feet” with cellulitis (n=8)—had progressed over 13.2±15.1 weeks. The preoperative work-up included: bacteriology samples 89%; standard x-rays of the foot 100% (osteitis 84%); duplex Doppler of the lower limb arteries 77% (tibial arteriopathy 87%); double bone scintigraphy 34% (osteitis 93%); TcPO2 (40±14mmHg); arteriography 27%; vascular surgery consultation 18%. Before surgery, 77% of the patients were hospitalised in an endocrinology unit (13±3 days) and 88% were on an antibiotic regimen for 26±18 days (50% i.v.). Orthopaedic surgery (without tourniquet, anaesthesia block, mean duration 53±24 min) involved: partial resection of a toe 23%; amputation of a ray 36% (first ray one, second ray five, third ray one, fourth ray two, fifth ray six); transmetatarsal amputation 32%; resection of the metatarsal heads 4%; calcanectomy (n=1); below knee amputation (n=1); and systematic and multiple samples for bacteriology (deep soft tissue and bone tissue) and for pathology. Results: Mean hospital stay in the surgery unit was 4±1 days, followed by 18±10 days in the endocrinology unit with antibiotics (oral for 88%) for 34±22 days, 91% of the lesions healed within 33±18 days; four required repeated procedures (two transmetatarsal amputations, one amputation of the first ray, one lower limb amputation); three lesions relapsed. The peroperative bacteriology samples of the deep soft tissue and bone tissue demonstrated, in comparison with the preoperative samples, that antibiotics had sterilised only 14% of the lesions; with discordant comparison in 40%, partial concordance in 24%, and total concordance in 24%. For the diagnosis of osteitis (confirmed by histology of peroperative bone samples), the x-ray interpretations were largely confirmed (79% exact diagnosis, 87% sensitivity, false positives 12%), as were the bone scintigrams with labelled polymorphonuclears (exact diagnosis 93%, sensitivity 93%, false positives 7%). Conclusion: This prospective study demonstrated the advantages of programmed surgery over emergency surgery, including for “acute feet”: limited resection, primary suture, rapid wound healing, short antibiotic treatment. It raises some questions concerning the validity of non-surgical bacteriological samples for perforating ulcers, even when performed under rigorous conditions (unique strain isolated from 76% of the samples) and on the possibility of antibiotic pressure on bacterial selection

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To investigate the impact of the Charlson and Elixhauser comorbidity indices on patient-reported outcomes measures (PROMs) following shoulder arthroplasty.

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Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties.

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COVID-19 necessitated abrupt changes in trauma service delivery. We compare the demographics and outcomes of patients treated during lockdown to a matched period from 2019. Findings have important implications for service development.

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The UK government declared a national lockdown on 23 March 2020 to reduce transmission of COVID-19. This study aims to identify the effect of lockdown on the rates, types, mechanisms, and mortality of musculoskeletal trauma across Scotland.

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Our objective is to describe our early and mid-term results with the use of a new simple primary knee prosthesis as an articulating spacer in planned two-stage management for infected knee arthroplasty. As a second objective, we compared outcomes between the group with a retained first stage and those with a complete two-stage revision.

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The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice.

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Despite declining frequency of blood transfusion and electrolyte supplementation following total joint arthroplasty, postoperative blood analyses are still routinely ordered for these patients. This study aimed to determine the rate of blood transfusion and electrolyte restoration in arthroplasty patients treated with a perioperative blood conservation protocol and to identify risk factors that would predict the need for transfusion and electrolyte supplementation.

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To our knowledge, there is currently no information available about the rate of venous thromboembolism (VTE) or recommendations regarding chemoprophylaxis for patients whose lower limb is immobilized in a plaster cast. We report a retrospective case series assessing the rate of symptomatic VTE in patients treated with a lower limb cast. Given the complex, heterogeneous nature of this group of patients, with many risk factors for VTE, we hypothesized that the rate of VTE would be higher than in the general population.

Objectives

The osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) balance is of the utmost importance in fracture healing. The aim of this study was therefore to investigate the impact of nonosteogenic factors on OPG and RANKL levels.

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The aim of this study was to determine whether patients with metal-on-metal (MoM) arthroplasties of the hip have an increased risk of cardiac failure compared with those with alternative types of arthroplasties (non-MoM).