Diabetes mellitus is a risk factor for complications after operative management of ankle fractures. Generally, diabetic sequelae such as neuropathy and nephropathy portend greater risk; however, the degree of risk resulting from these patient factors is poorly defined. We sought to evaluate the effects of the diabetic sequelae of neuropathy, chronic kidney disease (CKD), and peripheral vascular disease (PVD) on the risk of complications following operative management of ankle fractures. Using a national claims-based database we analyzed patients who had undergone operative management of an ankle fracture and who remained active in the database for at least two years thereafter. Patients were divided into two cohorts, those with a diagnosis of diabetes and those without. Each cohort was further stratified into five groups: neuropathy, CKD, PVD, multiple sequelae, and no sequelae. The multiple sequelae group included patients with more than one of the three sequelae of interest: CKD, PVD and neuropathy. Postoperative complications were queried for two years following surgery. The main complications of interested were: deep vein thrombosis (DVT), surgical site infection, hospital readmission within 90 days, revision internal fixation, conversion to ankle fusion, and below knee amputation (BKA). We identified 210,069 patients who underwent operative ankle fracture treatment; 174,803 had no history of diabetes, and 35,266 were diabetic. The diabetic cohort was subdivided as follows: 7,506 without identified sequelae, 8,994 neuropathy, 4,961 CKD, 1,498 PVD, and 12,307 with multiple sequelae. Compared to non-diabetics, diabetics without sequelae had significantly higher odds of DVT, infection, readmission, revision internal fixation and conversion to ankle fusion (OR range 1.21 – 1.58, p values range Compared to uncomplicated diabetics, diabetics with neuropathy alone and diabetics with multiple sequelae were found to have significantly higher odds of all complications (OR range 1.18 – 31.94, p values range < 0.001 - 0.034). Diabetics with CKD were found to have significantly higher odds of DVT, readmission, and BKA (OR range 1.34 – 4.28, p values range < 0.001 - 0.002). Finally, diabetics with PVD were found to have significantly higher odds of DVT, readmission, conversion to ankle fusion, and BKA (OR range 1.62 - 9.69, p values range < 0.001 - 0.039). Diabetic patients with sequelae of neuropathy, CKD or PVD generally had higher complication rates than diabetic patients without these diagnoses. Unsurprisingly, diabetic patients with multiple sequalae are at the highest risk of complications and had the highest odds ratios of all complications. While neuropathy is known to be associated with postoperative complications, our analysis demonstrates that CKD represents a significant risk factor for multiple complications following the operative management of ankle fractures and has rarely been discussed in prior studies

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

Introduction. Diabetes mellitus type 2 (DMT2) patients often develop Achilles tendon (AS) degeneration. The ZDF rat model is often used to study DMT2. Hence, this study investigated whether tenocytes isolated from diabetic and non diabetic ZDF rats respond differentially to normo- (NG) and hyperglycemic (HG) conditions in the presence of tumor necrosis (TNF)α. Method. AS tenocytes isolated from adult diabetic (fa/fa) or lean (fa/+) Zucker Diabetic Fatty (ZDF) rats were treated with 10 ng/mL TNFα either under NG or HG conditions (1 g/L versus 4.5 g/L glucose). Tendons were characterized histopathologically using Movin score. Tenocyte survival, metabolic activity, gene and/or protein expression of the main tendon extracellular matrix (ECM) component collagen type 1, the myofibroblast marker alpha smooth muscle actin (αSMA, Acta2), complement regulatory factors, the antioxidant defense enzyme heme oxygenase-1 (Hmox1), suppressors of cytokine signaling (Socs)1 and Soc3 were analyzed. Result. Tendons of diabetic rats showed significantly higher Movin score values suggesting tendon degeneration. Tenocyte vitality remained high, but metabolic activity was impaired by HG conditions, irrespectively of tenocyte origin. Higher amounts of αSMA were visualized in tendons/cells of diabetic rats or those exposed to TNFα. Collagen type 1 protein and gene expression was suppressed by TNFα (NG), but only in cells of non diabetic animals. The anaphylatoxin receptor C3aR was higher expressed in tenocytes from diabetic animals. CD46 was suppressed by TNFα (NG) in cells of diabetic rats. Hmox1, Socs1 and Socs3 were induced by HG, but only in tenocytes of diabetic rats (4 h). Conclusion. The response of tenocytes to TNFα depends on glucose supply and cell origin suggesting their irreversible impairment in DMT2

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

Introduction. There is a need for a standardised guideline to assist in optimal decision-making in diabetics who have acquired an ankle fracture. Through a critical analysis of the literature, a diagnostic and management algorithm that incorporates a quantitative scoring system is proposed and presented for consideration. Methods. Publications were identified by conducting a comprehensive keyword search of Medline, EMBASE and CINAHL databases. Search terms included “diabetes,” “ankle,” and “fracture”. Articles published in the English language that were pertinent to the topic were included. Manual search of the references in these relevant papers were also completed to further identify publications for potential inclusion. Publications and conferences not published in the English language or not pertinent to the topic in the above databases were excluded. Duplicate results that occurred in different databases were truncated to a single result. Results. A total of 352 results were revealed using the above methods. Of these, 59 articles met our inclusion criteria. 293 articles met our exclusion criteria. A further 9 articles were included after reviewing the included articles and their respective references. From these results, we propose a detailed diagnostic algorithm that may provide a systematic approach to a diabetic patient who presents with acute ankle pain, swelling, warmth, and/or redness. If a fracture is noted on plain radiographs, a proposed management algorithm and scoring system can be used to assist in deciding whether to proceed with primary open reduction, internal fixation (ORIF) or primary arthrodesis/rigid fixation. This scoring system is based on factors acquired through history and examination. Major factors have been allocated a score of 2, which include: previous or coinciding history of Charcot arthropathy, peripheral neuropathy, insulin dependence with poor compliance, and a diabetic history of greater than 20 years. Minor factors have been allocated a score of 1, which include: age > 50, nephropathy, retinopathy, osteoporosis, vasculopathy, and presence of nutrition/diet deficiency. A score of greater than 7 suggests a primary limb-salvage arthrodesis/rigid fixation because of the likely poor outcome in a primary ORIF. A score of less than 7 suggests that an acceptable outcome will likely result with a primary ORIF. Discussion. Through the use of the AFDA algorithm and score, it will hopefully provide a standardised approach to diabetic ankle fractures and; a method of quantifying risks for both the patient and affected ankle joint, thus, allowing the surgeon to have confidence in achieving the best possible outcome. Although this score is based on a critical analysis of the current literature, further validation of both this algorithm and score is recommended. Once validated, the AFDA score in particular, can also potentially be used as a research tool for further follow-up and outcome studies on diabetic ankle fractures

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. Methods. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro. Results. The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (Ccn2) in WT mouse cells. Conclusion. Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis. Cite this article: Bone Joint Res 2024;13(7):321–331

Osteoarthritis (OA) and diabetis mellitus type 2 (DMT2) are pathogenetically linked. Complement dysregulation contributes to OA and could be involved in DMT2. The inflammatory anaphylatoxin C5a is released during complement activation. This study aims to understand the specific responses of chondrocytes isolated from diabetic and non-diabetic rats exposed to C5a and/or the proinflammatory cytokine TNFα in vitro dependent on the glucose supply. Articular chondrocytes of adult Zucker Diabetic Fatty (ZDF) rats (homozygous: fa/fa, diabetic, heterozygous: fa/+, lean controls) were exposed to 10 ng/mL TNFα and 25 ng/mL C5a alone or in combination, both, under normo- (NG, 1 g/L glucose) and hyperglycemic (HG, 4.5 g/L glucose) conditions (4 or 24 h). Chondrocyte survival, metabolic activity and gene expression of collagen type 2, suppressors of cytokine signaling (SOCS)1, −3 and anti-oxidative hemoxygenase-1 (HMOX1) were assessed. The complement regulatory protein CD46 and cell nuclei sizes were analyzed. Chondrocyte vitality remained unaffected by the treatment. Metabolic activity was impaired in chondrocytes of non-diabetic rats under HG conditions. Collagen type 2 transcription was suppressed by TNFα under HG condition in chondrocytes from nondiabetic donors and under both conditions in those of DMT2 rats (24 h). Except for DMT2 chondrocytes under HG (4 h), HMOX1 was generally induced by TNFα +/- C5a (NG, HG). C5a elevated HMOX1 only in chondrocytes of controls. The SOCS1/3 genes were increased by TNFα (NG, diabetic, non diabetic, 4 and 24 h). This could also be observed in chondrocytes of diabetic, but not of lean rats (24 h, HG). At 4 h, C5a induced SOCS1 only in non diabetic chondrocytes (NG, HG). Cytoprotective CD46 protein was suppressed by TNFα under NG condition. Nuclear volumes of chondrocyte were lower in chondrocytes from DMT2 rats compared to those from controls. The differential response suggests that chondrocytes are irreversibly compromised by DMT2. Achnowledgement: The authors are grateful for the support by the “Stiftung Edoprothetik (S 04/21)”

Objectives. Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM. Methods. Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint. Results. Microarray analysis showed that there were 14 miRNAs at day five and 17 miRNAs at day 11, with a greater than twofold change in the DM group compared with the control group. Among these types of miRNA, five were selected based on a comparative and extended literature review. Real-time PCR analysis revealed that five types of miRNA (miR-140-3p, miR-140-5p, miR-181a-1-3p, miR-210-3p, and miR-222-3p) were differentially expressed with changing patterns of expression during fracture healing in diabetic rats compared with controls. Conclusions. Our findings provide information to further understand the pathology of impaired fracture healing in a diabetic rat model. These results may allow the potential development of molecular therapy using miRNA for the treatment of impaired fracture healing in patients with DM. Cite this article: S. Takahara, S. Y. Lee, T. Iwakura, K. Oe, T. Fukui, E. Okumachi, T. Waki, M. Arakura, Y. Sakai, K. Nishida, R. Kuroda, T. Niikura. Altered expression of microRNA during fracture healing in diabetic rats. Bone Joint Res 2018;7:139–147. DOI: 10.1302/2046-3758.72.BJR-2017-0082.R1

Aim. Forefoot ulcers in patients with diabetic neuropathy are a result of factors that result in increased forefoot plantar pressures. Progressive hindfoot equinus from contraction of gastrocnemius-soleus-tendo-Achilles complex and progressive plantar flexed metatarsal heads secondary to claw toe deformity results callus at the metatarsal heads which break down to ulceration. The aim is to describe 2-stage treatment pathway for managing these ulcers. Methods. Consecutive patients, who presented with forefoot ulcers since February 2019 were treated with a 2-stage treatment pathway. The first stage of this is an out-patient tendo-Achilles lengthening (TAL). The second stage is surgical proximal dorsal closing wedge metatarsal osteotomy for patients with persistent or recurrent ulcers. Patients were followed for a minimum of 12 months. Results. 112 patients (146 feet) underwent TAL by 3 consultants. Of these, 96 patients were followed for a minimum of 12 months (range 12–36 months). None had infection or wound related problems at the tenotomy sites; complete transection of the tendon was noted in 4 patients (4%) and one-patient developed heel callosity suggestive of over-lengthening. In 92 patients (96%), the ulcers healed within 10 weeks (± 4 weeks). Additional z-lengthening of peroneal longus and tibialis posterior tendons helped in patients with 1. st. metatarsal and 5. th. metatarsal head ulcers respectively. In 12 patients (10%), the ulcer failed to heal or recurred. MRI scan in these patients showed plantar flexed metatarsals from progressive claw toe deformity. The ulcer in this group healed after surgical offloading with proximal dorsal closing wedge osteotomy of the metatarsal/s, with no recurrence at a minimum 12months of follow-up. Conclusion. The described 2-stage treatment pathway results in long-term healing of neuropathic forefoot ulcers, and in 96% of patients, the ulcer healed after the first stage out-patient percutaneous TAL

Diabetes is a poor prognostic indicator after an acute ankle fracture. Many surgeons avoid essential surgery due to their concerns regarding complications. We performed a retrospective analysis of complication rates for acute ankle fractures in diabetics with a control non-diabetic patient treated by all surgeons in our unit and assessed factors for success including long-segment fixation methodologies. Patient records were cross-referenced with departmental databases and a retrospective review of all ankle fractures managed in our department was conducted from 2014. All patients subjected to a retrospective review of their notes and assessment of their follow up for at least 6 months. Radiographs were assessed of the ankle before and at completion of treatment were reviewed independently (RA and FR). We identified all patients with a diabetic ankle fracture their HB1Ac (for diabetic control) and systematic co-morbidities. Fractures were classified into unimalleolar, bi malleolar and trimalleolar and surgery grouped into standard or long-segment-rigid fixation. Statistical analysis was conducted using absolute/relative risk (RR); numbers needed to treat (NNT) were calculated. We compared a control-group, a diabetic group managed conservatively, and undergoing surgery; comparing the concept of rigid fixation. Further sub-analysis conducted to assess differences between diabetic neuropathy, retinopathy and nephropathy. Ethics approval was granted as per our institutional policy by our governance lead. We identified 64 patients with a diabetic ankle fractures, their fracture pattern and a control group. Thirty-one had conservative treatment; 33 had operative fixation of which 13 had rigid fixation. Compared to the control (n=32) both diabetic groups had a higher risk of possible complication. The relative risk was between 3.1–3.4 (P<0.002) and linked to systematic complications of diabetes e.g. neuropathy 5.9 (P<0.003); HBA1c 4.6 P<0.004); and neuropathy and retinopathy 6.2 P<0.0003). We observed RR is reduced for a complication occurring following surgery with prolonged immobilization (0.86) and rigid fixation (0.65) and NNT required to see a benefit from rigid fixation was 7. The overall RR for a complication was similar between conservative and surgical management (4.6 vs.5.1). We agree diabetics have a higher risk for complications than non-diabetics, however the risk is not as great as previously reported. There is little difference in surgical or conservative treatment but strong evidence indicating rigid long-segment-fixation with prolonged-immobilization could improve the risk benefit ratio when compared to non- operative management alone but further evaluation is required

Aim. To describe a 2-stage treatment pathway for managing neuropathic forefoot ulcers and the safety and efficacy of percutaneous tendo-Achilles lengthening (TAL) in out-patient clinics. Methods. Forefoot ulcers in patients with diabetic neuropathy are a result of factors that result in increased forefoot plantar pressure. Plantar flexed metatarsal heads secondary to progressive claw toe deformity and hindfoot equinus from changes within the gastrocnemius-soleus-tendo-Achilles complex, with additional contraction of tibialis posterior and peroneal longus, secondary to motor neuropathy results in progressive increase in forefoot plantar pressures. Consecutive patients, who presented to our Diabetic Foot clinic since February 2019 with forefoot ulcers or recurrent forefoot callosity were treated with TAL in the first instance, and in patients with recurrent or non-healing ulcers, by proximal dorsal closing wedge osteotomy; a 2-stage treatment pathway. Patients were followed up at 3, 6, and 12 months to assess ulcer healing and recurrence. Results. One hundred and twelve patients (146 feet) underwent TAL by 3 consultants in the out-patient clinics. Of these, 96 feet were followed for a minimum of 12 months (range 12–36 months). None had infection or wound related problems at the tenotomy sites; complete transection of the tendon was noted in 4 patients (4%) and one-patient developed heel callosity suggestive of over-lengthening. In 92 feet (96%), the ulcers healed within 10 weeks (± 4 weeks). Additional z-lengthening of peroneal longus and tibialis posterior tendons helped in patients with big-toe and 5. th. metatarsal head ulcers. In 12 feet (10%), the ulcer failed to heal or recurred, the MRI scan in these patients showed plantar flexed metatarsals secondary to progressive claw toe deformity. The ulcer in this group healed after surgical offloading with proximal dorsal closing wedge osteotomy. In patients with osteomyelitis, the intramedullary canal was curetted and filled with local antibiotic eluting agents such as Cerament G. ®. The osteotomy site was stabilised with a percutaneous 1.6mm k-wire. Conclusion. The described 2-stage treatment pathway results in long-term healing of neuropathic forefoot ulcers, and in 96% of patients, the ulcer healed after out-patient percutaneous TAL alone. TAL is a safe and effective initial out-patient procedure with improved patient outcomes

This study aims to assess the fracture mechanics of type-2 diabetic (T2D) femoral bone using innovative site-specific tests, whilst also examining the cortical and trabecular bone microarchitecture from various regions using micro-computed tomography (CT) of the femur as the disease progresses. Male [Zucker Diabetic Fatty (ZDF: fa/fa) (T2D) and Zucker Lean (ZL: fa/+) (Control)] rats were euthanized at 12-weeks of age, thereafter, right and left femora were dissected (Right femora: n = 6, per age, per condition; Left femora: n=8-9, per age, per condition). Right femurs were notched in the posterior of the midshaft. Micro-CT was used to scan the proximal femur, notched and unnotched femoral midshaft (cortical) of the right femur and the distal metaphysis (trabecular) of the left femur to investigate microarchitecture and composition. Right femurs were fracture toughness tested to measure the stress intensity factor (Kic) followed by a sideways fall test using a custom-made rig to investigate femoral neck mechanical properties. There was no difference in trabecular and cortical tissue material density (TMD) between T2D and control rats. Cortical thickness was unchanged, but trabeculae were thinner (p<0.01) in T2D rats versus controls. However, T2D rats had a greater number of trabeculae (p<0.05) although trabecular spacing was not different to controls. T2D rats had a higher connectivity distribution (p<0.05) and degree of anisotropy (p<0.05) in comparison to controls. There was no difference in the mechanical properties between strains. At 12-weeks of age, rats are experiencing early-stage T2Ds and the disease impact is currently not very clear. Structural and material properties are unchanged between strains, but the trabecular morphology shows that T2D rats have more trabecular struts present in order to account for the thinner trabeculae

Recent studies have shown that bone mineral distribution is more heterogeneous in bone tissue from an animal model of osteoporosis and osteoporotic human vertebral trabeculae. These tissue alterations may play a role in bone fragility seen in osteoporosis, albeit that they are not detectable by current diagnostic techniques (dual-energy X-ray absorptiometry, DXA). Type II Diabetes Mellitus (T2DM) also increases a patient's fracture risk beyond what can be explained or diagnosed by DXA, and is associated with impaired bone cell function, compromised collagen structure and reduced mechanical properties. However, it is not currently known whether osteoporosis or T2DM leads to an increased mineral heterogeneity in the femoral head of humans, a common osteoporotic fracture site. In this study, we examine bone microarchitecture, mineralisation and mechanical properties of trabecular bone from osteoarthritic, diabetic and osteoporotic patients. We report that while osteoporotic trabecular bone has significantly deteriorated mechanical properties and microarchitecture compared to the other groups, there is also a significant increase in mean mineral content. Moreover, the heterogeneity of the mineral content in osteoporotic bone is significantly higher than osteoarthritic (+35%) and diabetic (+13%) groups. We propose that the compromised architecture following bone loss at the onset of osteoporosis alters the mechanical environment, which initiates compensatory changes in mineral content. We show for the first time that trabecular bone mineralisation is significantly more heterogeneous (+20%) in T2DM compared to osteoarthritic controls. Interestingly, bone microarchitecture and mechanical properties are not significantly different between diabetic and osteoarthritic groups despite this increase in mineral heterogeneity

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

Introduction: We have previously reported on an incidence of diabetic amputations of 4, 4 per 1.000 diabetic subjects per year in the city of Trondheim, Norway, 1994–1997. As a consequence of that study, Trondheim Diabetic Foot Team was established January 1st 1996. The Diabetic Foot Team has been an integrated part of the Outpatient clinic, Department of Orthopaedic Surgery, St. Olavs University Hospital. We report on the incidence of diabetic amputations ten years later (2004–2007). Material and Methods: The University Hospital is the only hospital in Trondheim, and all amputations are performed at the Department of Orthopaedic Surgery. In 2004–2007 we registered consecutively all diabetic amputations. During the two study periods, 1994–1997 and 2004–2007, the population of Trondheim was 143.300 and 159.000 inhabitants, respectively. The total number of diabetic subjects in Trondheim during the two study periods was 3.600 and 4.600, respectively. Changes in incidence rates were analyzed using Poisson regression with decade as covariate. Two sided p-values < 0.05 were considered significant. Analyses were performed in State version10.0. Results: During the decade the number of diabetic amputations/1000 diabetics/year decreased 40 percent from 4, 4 to 2, 8 (p= 0.04). In the same period, 779 patients with diabetes were screened at the Diabetic Foot Team, and 5915 consultations due to diabetic foot problems were performed. From 1996 to 2006 the number of invasive and non-invasive vascular intervention per year in patients with diabetes living in Trondheim did not change. Discussion: Although other factors may be involved, we attribute the decrease in the incidence of diabetic amputations to the activity of the Diabetic Foot Team. Every department of orthopaedic surgery should make priority to the implementation of a multidisciplinary program for prevention and treatment of diabetic foot ulcers

Abstract. The aim is to describe the safety and efficacy of TAL in out-patient clinics when managing diabetic forefoot ulcers. Patients and Methods. Consecutive patients, who underwent TAL and had minimum 12m follow-up were analysed. Forceful dorsiflexion of ankle was avoided and patients were encouraged to walk in Total contact cast for 6-weeks and further 4-weeks in walking boot. Results. 142 feet in 126 patients underwent this procedure and 86 feet had minimum follow-up of 12m. None had wound related problems. Complete transection of the tendon was noted in 3 patients and one-patient developed callosity under the heel. Ulcers healed in 82 feet (96%) within 10 weeks however in 12 feet (10%), the ulcer recurred or failed to heal. MRI showed plantar flexed metatarsals with joint subluxation. The ulcer in this subgroup healed following proximal dorsal closing wedge osteotomy. Conclusion. Tightness of gastroc-soleus-Achilles complex and subluxed MTP joint from soft tissue changes due to motor neuropathy result in increased forefoot plantar pressures. A 2-stage approach as described result in long-term healing of forefoot ulcers, and in 96% of patients, the ulcer healed following TAL alone. TAL is a safe and effective out-patient procedure with improved patient satisfaction outcomes

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

Introduction. Total contact casting (TCC) is one of the most commonly utilized modalities in the management of diabetic feet. We undertook a retrospective review to determine the prevalence of symptomatic VTE events in patients treated in a weight bearing TCC in our diabetic foot unit, and to formulate guidelines for VTE prophylaxis. Methods. Electronic records were reviewed to identify all patients treated in a TCC between 2014 and 2021. Data collection included patient demographics, comorbidities, period of immobilization in TCC, the incidence of VTE events, and any VTE prophylaxis prescribed during their period in TCC. Results. 549 patients were identified who had at least one episode of TCC. Mean age was 67 years (range 28 to 94 years) and the mean duration in cast was 10.2 weeks (range 0.3–46 weeks). Only 6 patients (1.1%) were prescribed chemical thrombo-prophylaxis during their period in TCC. Mean body mass index (BMI) for these patients was 32.3 (Range 18.4–58.9). Other significant comorbidities: 81% (n-444) of patients had associated cardio-vascular comorbidities; 54 % (n-296) had renal comorbidities including 22% (n-121) having had dialysis and 4.2% (n-23) with renal transplants. Eight of the 549 patients (1.5%) had suffered a VTE event of which only 2 (0.36%) were during the period of immobilization in TCC. One was a symptomatic DVT (0.18%) and the another was an asymptomatic (incidental) finding of pulmonary embolism (PE). There was no mortality related to the VTE episodes. Conclusion. NICE guidelines state that one should “Consider pharmacological VTE prophylaxis for patients with lower limb immobilization”. Our study finds that patients treated in a weight bearing TCC do not require routine pharmacological VTE prophylaxis, in spite of an extended period of lower limb immobilization and significant medical comorbidities

Aim. To assess the spread of foot infection and its impact on the outcomes of major amputations of lower extremities in diabetic patients. Method. In a multicentre retrospective and prospective cohort study, we included adult diabetic patients (≥ 18 years) who underwent a major amputation of a lower limb in 5 hospitals between 2000 and 2009, 2012 and 2014. A total of 51 patients were included (of which 27 (52.94%) were men and 24 (47.06%) were women) with the mean age of 65.51 years (SD=16.99). Concomitant section's osseous slice biopsy (BA) and percutaneous bone biopsy of the distal site (BD) were performed during limb amputation. A new surgical set-up and new instruments were used to try and reduce the likelihood of cross-contamination during surgery. A positive culture was defined as the identification of at least 1 species of bacteria not belonging to the skin flora or at least 2 bacteria belonging to the skin flora (CoNS (coagulase negative staphylococci), Corynebacterium spp, Propionibacterium acnes) with the same antibiotic susceptibility profiles. A doubtful culture was defined as the identification of 1 species of bacteria belonging to the skin flora. The patients were followed-up for 1 year. Stump outcomes were assessed on the delay of complete healing, equipment, need of re-intervention and antibiotics. Results. In total, 51 BA were performed during major lower limb amputations (17 above the knee and 34 below the knee) in diabetic patients. Nine (17.65%) bacterial culture results from BA specimens were positive, 7 (13.73%) doubtful and 35 (68.63%) sterile. Before amputation, 23 patients (45.1%) had not received any antibiotics, including 16 (31.37%) with an antibiotic-free interval of 15 days or more. Microorganisms identified in BA were also cultured from the distal site in 33.33% of the cases. Positive BA was associated with prolonged complete stump healing, delay of complete healing (more than 6 months), re-amputation and the need of antibiotics. Conclusions. The microorganisms identified from BA play a role in stump healing in diabetic patients. BA is useful during major limb amputation due to infectious complications and antibiotic therapy could be corrected on the basis of the BA culture results

Diabetes is a poor prognostic indicator after an ankle fracture. Many surgeons avoid operating due to concerns regarding complications. We performed a retrospective analysis of complication rates for acute ankle fractures in diabetics with a control non-diabetic patient treated by all surgeons in our unit and assessed factors for success including long-segment fixation. Patient records were cross-referenced with departmental databases and a review of all ankle fractures managed in our department was conducted from 2012. All patients subjected to a retrospective-review of their follow-up for at least 6-months. Radiographs were assessed of the ankle before and at completion of treatment being reviewed independently (RA & FR). We identified the HB1Ac (diabetic-control) and systematic co-morbidities. Fractures were classified into unimalleolar, bi malleolar and trimalleolar and surgery grouped into standard or long-segment-rigid fixation. Statistical analysis was conducted using absolute/relative risk (RR); numbers needed to treat (NNT) were calculated. We compared a control-group, a diabetic group managed conservatively, and undergoing surgery; comparing the concept of rigid fixation and prolonged imobilisation in isolation or combined. Further sub-analysis conducted assessing diabetic neuropathy, retinopathy and nephropathy. Ethics approval was granted as per our institutional policy by our governance lead. We identified 154 diabetic ankle fractures, seventy-six had conservative-treatment; 78 had operative fixation of which 23 had rigid-long-segment-fixation. The diabetic-groups had a higher risk-relative-risk of complication − 3.2 (P< 0.03) being linked to systematic complications of diabetes e.g. neuropathy 5.8 (P< 0.003); HBA1c 4.6 P< 0.004); and neuropathy or retinopathy 6.2 (P< 0.0003). Relative-risk reduction of complications occurred following surgery with prolonged immobilization (0.86) and rigid-fixation (0.65). The Number-Needed-to-Treat required to see a benefit from rigid fixation was 7. Diabetics have a higher risk for complications, however the risk is not as great as previously reported. We provide evidence of rigid-long-segment-fixation with prolonged-immobilization improving-outcomes