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

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)”

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

Long bone fractures in patients with diabetes mellitus (DM) are slow to heal, often resulting in delayed reunion or non-union. It is reasonable to postulate that the underlying cause of these DM-associated complications is a reduced population of bone marrow progenitor cells and/or their dysfunction. With the hypothesis that the administration of healthy, allogeneic adult bone marrow-derived mesenchymal stromal cells (MSCs) can enhance DM fracture healing, the aim of this endeavour was to assess the efficacy of MSC administration to support fracture repair using two doses. Here 250,000 or 500,000 human bone marrow-derived MSCs were locally introduced to femoral fractures in diabetic mice, and the quality of de novo bone assessed 8 weeks later. Preliminary bone bridging was evident in all animals; however, a large circumferential reparative callus was consistently retained indicating non-union. Micro-CT analysis elucidated consistent callus dimensions, bone mineral density, bone volume/total volume in all groups, but an increase in bone surface area/bone volume in cell-treated fractures. Moreover, greater amounts of mature bone were identified in fractures treated with a low dose of MSCs. Four-point bending evaluation of the mechanical integrity of the repairing fracture indicated a statistically significant improvement in flexure strength and flexure modulus in DM fractures treated with 250,000 MSCs as compared to controls. An improvement in total energy required for failure was observed in both groups that received MSCs. Therefore, the administration of non-DM bone marrow-derived MSCs supported the development of more mature bone in the reparative callus, resulting in greater mechanical integrity

Differences at motor control strategies to provide dynamic balance in various tasks in diabetic polyneuropatic (DPN) patients due to losing the lower extremity somatosensory information were reported in the literature. It has been stated that dynamics of center of mass (CoM) is controlled by center of pressure (CoP) during human upright standing and active daily movements. Indeed analyzing kinematic trajectories of joints unveil motor control strategies stabilizing CoM. Nevertheless, we hypothesized that imbalance disorders/CoM destabilization observed at DPN patients due to lack of tactile information about the base of support cannot be explained only by looking at joint kinematics, rather functional foot usage is proposed to be an important counterpart at controlling CoM. In this study, we included 14 DPN patients, who are diagnosed through clinical examination and electroneuromyography, and age matched 14 healthy subjects (HS) to identify control strategies in functional reach test (FRT). After measuring participants’ foot arch index (FAI) by a custom-made archmeter, they were tested by using a force plate, motion analysis system, surface electromyography and pressure pad, all working in synchronous during FRT. We analyzed data to determine effect of structural and functional foot pathologies due to neuropathy on patient performance and postural control estimating FAI, reach length (FR), FR to height (H) ratio (FR/H; normalized FR with respect to height), displacement of CoM and CoP in anteroposterior direction only, moment arm (MA, defined as the difference between CoP and CoM at the end of FRT), ankle, knee and hip joint angles computed at the sagittal plane for both extremities. Kinematic metrics included initial and final joint angles, defined with respect to start and end of reaching respectively. Further difference in the final and initial joint angles was defined as Δ. FAI was founded significantly lower in DPN patients (DPN: 0.3404; HS: 0.3643, p= <0.05). The patients’ FR, FR/H and absolute MA and displacement of CoM were significantly shorter than the control group (p= <0.05). Displacement of CoP between the two groups were not significant. Further we observed that CoM was lacking CoP in DPN patients (mean MA: +0.88 cm), while leading CoP in HS (mean MA: −1.59 cm) at the end of FRT. All initial angles were similar in two groups, however in DPN patients final right and left hip flexion angle (p=0.016 and p=0.028 respectively) and left ankle plantar flexion angle (p=0.04) were smaller than HS significantly. DPN patients had significantly less (p=0.029) hip flexion (mean at right hip angle, Δ=25.0°) compared to HS (Δ=33.53°) and ankle plantar flexion (DPN mean at right ankle angle, Δ=6.42°, HS mean Δ=9.07°; p=0.05). The results suggest that movement of both hip and ankle joints was limited simultaneously in DPN patients causing lack of CoM with respect to CoP at the end of reaching with significantly lower FAI. These results lead to the fact that cutaneous and joint somatosensory information from foot and ankle along with the structure of foot arch may play an important role in maintaining dynamic balance and performance of environmental context. In further studies, we expect to show that difference at control strategies in DPN patients due to restricted functional foot usage might be a good predictor of how neuropathy evolves to change biomechanical aspects of biped erect posture

Fragility ankle fractures are traditionally managed conservatively or with open reduction internal fixation (ORIF). Tibiotalocalcaneal (TTC) fusion is an alternative option for the geriatric patient. This systematic review and meta-analysis provides a detailed analysis of the functional and clinical outcomes of hindfoot nailing for fragility ankle fractures presented so far in the literature. A systematic search was performed on MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science, identifying fourteen studies for inclusion. Studies including patients over 60 with a fragility ankle fracture, treated with TTC nail were included. Patients with a previous fracture of the ipsilateral limb, fibular nails, and pathological fractures were excluded. Subgroup analyses were performed according to (1) open vs closed fractures, (2) immediate post-operative FWB vs post-operative NWB, (3) majority of cohort are diabetics vs minority of cohort are diabetics. Meta-regression analyses were done to explore sources of heterogeneity, and publication bias was assessed using Egger's test. The pooled proportion of superficial infection, deep infection, implant failure, malunion, and all-cause mortality was 0.10 (95%CI:0.06-0.16; I2=44%), 0.08 (95%CI:0.06-0.11, I2=0%), 0.11 (95%CI:0.07-0.15, I2=0%), 0.11 (95%CI:0.06-0.18; I2=51%), and 0.27 (95%CI:0.20-0.34; I2=11%), respectively. The pooled mean post-operative OMAS score was 54.07 (95%CI:48.98-59.16; I2=85%). The best-fitting meta-regression model included age and percentage of male patients as covariates (p=0.0263), and were inversely correlated with higher OMAS scores. Subgroup analyses showed that studies with a majority of diabetics had a higher proportion of implant failure (p=0.0340) and surgical infection (p=0.0096), and a lower chance of returning to pre-injury mobility than studies with a minority of diabetics (p=0.0385). Egger's test (p=0.56) showed no significant publication bias. TTC nailing is an adequate alternative option for fragility ankle fractures. However, current evidence includes mainly case series with inconsistent outcome measures reported and post-operative rehabilitation protocols. Prospective RCTs with long follow-up times and large cohort sizes are needed to clearly guide the use of TTC nailing for ankle fractures

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

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

3D accurate measurements of the skeletal structures of the foot, in physiological and impaired subjects, are now possible using Cone-Beam CT (CBCT) under real-world loading conditions. In detail, this feature allows a more realistic representation of the relative bone-bone interactions of the foot as they occur under patient-specific body weight conditions. In this context, varus/valgus of the hindfoot under altered conditions or the thinning of plantar tissues that occurs with advancing age are among the most complex and interesting to represent, and numerous measurement proposals have been proposed. This study aims to analyze and compare these measurements from CBCT in weight-bearing scans in a clinical population. Sixteen feet of diabetic patients and ten feet with severe adult flatfoot acquired before/after corrective surgery underwent CBCT scans (Carestream, USA) while standing on the leg of interest. Corresponding 3D shapes of each bone of the shank and hindfoot were reconstructed (Materialise, Belgium). Six different techniques found in the literature were used to calculate the varus/valgus deformity, i.e., the inclination of the hindfoot in the frontal plane of the shank, and the distance between the ground and the metatarsal heads was calculated along with different solutions for the identification of possible calcifications. Starting with an accurate 3D reconstruction of the skeletal structures of the foot, a wide range of measurements representing the same angle of hindfoot alignment were found, some of them very different from each other. Interesting correlations were found between metatarsal height and subject age, significant in diabetic feet for the fourth and fifth metatarsal bones. Finally, CBCT allows 3D assessment of foot deformities under loaded conditions. The observed traditional measurement differences and new measurement solutions suggest that clinicians should consider carefully the anatomical and functional concepts underlying measurement techniques when drawing clinical and surgical conclusions

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

An international Consensus Group has by a Delphi approach identified the topic of host factors affecting pin site infection to be one of the top 10 priorities in external fixator management. The aim of this study was to report the frequency of studies reporting on specific host factors as a significant association with pin site infection. Host factors to be assessed was: age, smoking, BMI and any comorbidity, diabetes, in particular. The intention was an ethological review, data was extracted if feasible, however no meta-analysis was performed. A systematic literature search was performed according to the PRISMA-guidelines. The protocol was registered before data extraction in PROSPERO. The search string was based on the PICO criterias. A logic grid with key concept and index terms was made. A search string was built assisted by a librarian. The literature search was executed in three electronic bibliographic databases, including Embase MEDLINE (1111 hits) and CINAHL (2066 hits) via Ovid and Cochrane Library CENTRAL (387 hits). Inclusion criteria: external fixation, >1 pin site infection, host factor of interest, peer-reviewed journal. Exclusion criteria: Not written in English, German, Danish, Swedish, or Norwegian, animal or cadaveric studies, location on head, neck, spine, cranium or thorax, editorials or conference abstract. The screening process was done using Covidence. A total of 3564 titles found. 3162 excluded by title and abstract screening. 140 assessed for full text eligibility. 11 studies included for data extraction. The included studies all had a retrospective design. Three identified as case-control studies. Generally the included studies was assessed to have a high risk of bias. A significant associations between pin site infection for following host factors: a) increased HbA1C level in diabetic patients; b) congestive heart failure in diabetic patients; c) less co-morbidity; d) preoperative osteomyelitis was found individually. This systematic literature search identified a surprisingly low number of studies examining for risk of pin site infection and host factors. Thus, this review most of all serves to demonstrate a gap of evidence about correlation between host factors and risk of pin site infection, and further studies are warranted

Objectives. The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. Methods. Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined. Results. In tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased. Conclusion. This study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes. Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362–372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2

Despite considerable legacy issues, Girdlestone's Resection Arthroplasty (GRA) remains a valuable tool in the armoury of the arthroplasty surgeon. When reserved for massive lysis in the context of extensive medical comorbidities which preclude staged or significant surgical interventions, and / or the presence of pelvic discontinuity, GRA as a salvage procedure can have satisfactory outcomes. These outcomes include infection control, pain control and post-op function. We describe a case series of 13 cases of GRA and comment of the indications, peri, and post-operative outcomes. We reviewed all cases of GRA performed in our unit during an 8 year period, reviewing the demographics, indications, and information pertaining to previous surgeries, and post op outcome for each. Satisfaction was based on a binary summation (happy/unhappy) of the patients’ sentiments at the post-operative outpatient consultations. 13 cases were reviewed. They had a mean age of 75. The most common indication was PJI, with 10 cases having this indication. The other three cases were performed for avascular necrosis, pelvic osteonecrosis secondary to radiation therapy and end stage arthritis on a background of profound learning disability in a non-ambulatory patient. The average number of previous operations was 5 (1-10). All 13 patients were still alive post girdlestone. 7 (54%) were satisfied, 6 were not. 3 patients were diabetic. 5 patients developed a sinus tract following surgery. With sufficient pre-op patient education, early intensive physiotherapy, and timely orthotic input, we feel this procedure remains an important and underrated and even compassionate option in the context of massive lysis and / or the presence of pelvic discontinuity / refractory PJI. GRA should be considered not a marker of failure but as a definitive procedure that gives predictability to patients and surgeon in challenging situations

Type-2 Diabetic (T2D) patients experience up to a 3-fold increase in bone fracture risk[1]. Paradoxically, T2D-patients have a normal or increased bone mineral density when compared to non-diabetic patients. This implies that T2D has a deleterious effect on bone quality, whereby the intrinsic material properties of the bone matrix are altered. Creating clinical challenges as current diagnostic techniques are unable to accurately predict the fracture probability in T2D-patients. To date, the relationship between cyclic fatigue loading, mechanical properties and microdamage accumulation of T2D-bone tissue has not yet been examined and thus our objective is to investigate this relationship. Ethically approved femoral heads were obtained from patients, with (n=8) and without (n=8) T2D. To obtain the mechanical properties of the sample, one core underwent a monotonic compression test to 10% strain, the other core underwent a cyclic compression test at a normalized stress ratio between 0.0035mm/mm and 0.016mm/mm to a maximum strain of 3%. Microdamage was evaluated by staining the tissue with barium sulfate precipitate [2] and conducting microcomputed tomography scanning with a voxel size of 10μm. The monotonically tested T2D-group showed no statistical difference in mechanical properties to the non-T2D-group, even when normalised against BV/TV. There was also no difference in BV/TV. For the cyclic test, the T2D-group had a significantly higher initial modulus (p<0.01) and final modulus (p<0.05). There was no difference in microdamage accumulation. Previous population-level studies have found that T2D-patients have been shown to have an increased fracture risk when compared to non-T2D-patients. This research indicates that T2D does not impair the mechanical properties of trabecular bone from the femoral heads of T2D-patients, suggesting that other mechanisms may be responsible for the increased fracture risk seen in T2D-patients

To determine risk factors of infection in total knee arthroplasty. This descriptive study was conducted in the Department of Orthopedics for a duration of three years from January 2016 to January 2019. All patients undergoing primary total knee replacement were included in the study. Exclusion criteria were all patients operated in another hospital and revision total knee replacement. All patients were followed up at 2, 4, 8, 12 and 24 weeks post-operatively. Signs of inflammation and inflammatory markers such as total leukocyte count (TLC), C-reactive protein (CRP) and ESR were measured. Risk factors like age, body mass index (BMI), ASA, co-morbid conditions were also noted. A total of 78 patients underwent primary unilateral Total Knee Replacement (TKR) during the study period. Of these, 30 (34.09%) were male and 48 (61.54%) female patients. Mean age of patients was 68.32 ± 8.54 years. Average BMI 25.89 Kg/m2 .Osteoarthritis was the pre-dominant cause of total knee replacement (94.87%). Among co-morbid factors 33.33% were diabetic, 28.20% having ischemic heart disease and 12.82% with chronic lung disease. Upon anaesthesia fitness pre-operatively, 91.02% patients had an American society of anaesthesiologist score (ASA) between 0–2 while 07 (8.97%) between 3- 5. Average duration of surgery was 85.62± 4.11 minutes. 6.41% cases got infected. In majority of the infected cases (60%), Staphylococcus aureus was the infective organism. Diabetes Mellitus (p=0.01) and Obesity (p=0.02) had a significant relation to post-operative infection. Pre-operative risk evaluation and prevention strategies along with early recognition of infection and control can greatly reduce the risk of joint infection post-TKR which will not only improve the mobility of patient but also its morbidity and mortality as well. Key Words:. C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), Staphylococcus aureus, Total Knee Arthroplasty (TKA)

Fragility ankles fractures in the geriatric population are challenging to manage, due to fracture instability, soft tissue compromise, patient co-morbidities. Traditional management options include open reduction internal fixation, or conservative treatment, both of which are fraught with high complication rates. We aimed to present functional outcomes of elderly patients with fragility ankle fractures treated with tibiotalocalcaneal nails. 171 patients received a tibiotalocalcaneal nail over a six-year period, but only twenty met the inclusion criteria of being over sixty and having poor bone stock, verified by radiological evidence of osteopenia or history of fragility fractures. Primary outcome was mortality risk from co-morbidities, according to the Charlson co-morbidity index (CCI), and patients’ post-operative mobility status compared to pre-operative mobility. Secondary outcomes include intra-operative and post-operative complications, six-month mortality rate, time to mobilisation and union. The mean age was 77.82 years old, five of whom are type 2 diabetics. The average CCI was 5.05. Thirteen patients returned to their pre-operative mobility state. Patients with low CCI are more likely to return to pre-operative mobility status (p=0.16; OR=4.00). Average time to bone union and mobilisation were 92.5 days and 7.63 days, respectively. Mean post-operative AOFAS ankle-hindfoot and Olerud-Molander scores were 53.0 (range 17-88) and 50.9 (range 20-85), respectively. There were four cases of broken distal locking screws, and four cases of superficial infection. Patients with high CCI were more likely to acquire superficial infections (p=0.264, OR=3.857). There were no deep infections, periprosthetic fractures, nail breakages, non-unions. TTC nailing is an effective treatment methodology for low-demand geriatric patients with fragility ankle fractures. This technique leads to low complication rates and early mobilisation. It is not a life-changing procedure, with many able to return to their pre-operative mobility status, which is important for preventing the loss of socioeconomic independence

Open tibial fractures can be difficult to manage, with a range of factors that could affect treatment and outcome. We present a large cohort of patients, and analyse which factors have significant associations with infection outcome. Elucidation will allow clinicians to strive for treatment optimisation, and patients to be advised on likely complications. Open tibia fractures treated at a major trauma centre between 2015-2021 were included. Mean age at injury was 55.4 (range 13-102). Infection status was categorized into no infection, superficial infection, and osteomyelitis. Age, mode of injury, polytrauma, fibula status, Gustilo-Anderson (GA) classification, wound contamination, time from injury to: first procedure/definitive plastics procedure/definitive fixation, type of definitive fixation, smoking and diabetic status, and BMI, were collected. Multicollinearity was calculated, with highly correlated factors removed. Multinomial logistic regression was performed. Chi Squared testing, with Post Hoc Bonferroni correction was performed for complex categorical factors. Two hundred forty-four patients with open tibial fractures were included. Forty-five developed superficial infection (18.4%), and thirty-nine developed osteomyelitis (16.0%). Polytrauma, fibula status, and type of definitive fixation were excluded from the multivariate model due to strong multicollinearity with other variables. With reference to the non-infected outcome; superficial infection patients had higher BMI (p<0.01), higher GA grade (p<0.01), osteomyelitis patients had longer time to definitive fixation (p=0.049) and time to definitive plastics procedure (p=0.013), higher GA grade (p<0.01), and positive wound contamination(p=0.015). Poc hoc analysis showed “no infection” was positively associated with GA-I (p=0.029) and GA-II (p<0.01), and negatively associated with GA-IIIC (p<0.01). Osteomyelitis was positively associated with GA-IIIc (p<0.01). This study investigated the associations between the injury and presentation factors that may affect infection outcome. The variables highlighted are the factors clinicians should give extra consideration to when treating cases, and take preventative measures to optimize treatment and mitigate infection risk

Biomedical imaging is essential in the diagnosis of musculoskeletal pathologies and postoperative evaluations. In this context, Cone-Beam technology-based Computed Tomography (CBCT) can make important contributions in orthopaedics. CBCT relies on divergent cone X-rays on the whole field of view and a rotating source-detector element to generate three-dimensional (3D) volumes. For the lower limb, they can allow acquisitions under real loading conditions, taking the name Weight-Bearing CBCT (WB-CBCT). Assessments at the foot, ankle, knee, and at the upper limb, can benefit from it in situations where loading is critical to understanding the interactions between anatomical structures. The present study reports 4 recent applications using WB-CBCT in an orthopaedic centre. Patient scans by WB-CBCT were collected for examinations of the lower limb in monopodal standing position. An initial volumetric reconstruction is obtained, and the DICOM file is segmented to obtain 3D bone models. A reference frame is then established on each bone model by virtual landmark palpation or principal component analysis. Based on the variance of the model point cloud, this analysis automatically calculates longitudinal, vertical and mid-lateral axes. Using the defined references, absolute or relative orientations of the bones can be calculated in 3D. In 19 diabetic patients, 3D reconstructed bone models of the foot under load were combined with plantar pressure measurement. Significant correlations were found between bone orientations, heights above the ground, and pressure values, revealing anatomic areas potentially prone to ulceration. In 4 patients enrolled for total ankle arthroplasty, preoperative 3D reconstructions were used for prosthetic design customization, allowing prosthesis-bone mismatch to be minimized. 20 knees with femoral ligament reconstruction were acquired with WB-CBCT and standard CT (in unloading). Bone reconstructions were used to assess congruency angle and patellar tilt and TT-TG. The values obtained show differences between loading and unloading, questioning what has been observed so far. Twenty flat feet were scanned before and after Grice surgery. WB-CBCT allowed characterization of the deformity and bone realignment after surgery, demonstrating the complexity and multi-planarity of the pathology. These applications show how a more complete and realistic 3D geometric characterization of the of lower limb bones is now possible in loading using WB-CBCT. This allows for more accurate diagnoses, surgical planning, and postoperative evaluations, even by automatisms. Other applications are in progress