Quantitative ultrasound (QUS) is a promising tool to estimate bone structure characteristics and predict fragile fracture. The aim of this pilot cross-sectional study was to evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragile fractures retrospectively in postmenopausal women. Methods. RF signal and speed of sound (SOS) were obtained using an axial transmission QUS at one‐third distal radius for 246 postmenopausal women. Based on the involved RF signal, we conducted a MResNet, which combines multi-channel training with original ResNet, to classify the high risk of fragility fractures patients from all subjects. The bone mineral density (BMD) at lumber, hip and femoral neck acquired with DXA was recorded on the same day. The fracture history of all subjects in adulthood were collected. To assess the ability of the different methods in the discrimination of fragile fracture, the odds ratios (OR) calculated using binomial logistic regression analysis and the area under the receiver operator characteristic curves (AUC) were analyzed. Results. Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was discriminant for all fragile fractures (OR = 2.64; AUC = 0.74), for Vertebral fracture (OR = 3.02; AUC = 0.77), for non-vertebral fracture (OR = 2.01; AUC = 0.69). MResNet showed comparable performance to that of BMD of hip and lumbar with all types of fractures, and significantly better performance than SOS all types of fractures. Conclusions. the MResNet model based on the ultrasonic RF signal can significantly improve the ability of QUS device to recognize previous fragile fractures. Moreover, the performance of the proposed model modified by age, weight, and height is further optimized. These results open perspectives to evaluate the risk of fragile fracture applying a deep learning model to analyze ultrasonic RF signal

Osteoporosis is a disease when bone mass and tissue is lost, with a consequent increase in bone fragility and increase susceptibility to develop fracture. The osteoporosis prevalence increases markedly with age, from 2% at 50 years to more than 25% at 80 years. 1. in women. The vast majority of distal radius fractures (DRFs) can be considered fragility fractures. The DRF is usually the first medical presentation of these fractures. With an aging population, all fracture clinics should have embedded screening for bone health and falls risk. DRF is the commonest type of fracture in perimenopausal women and is associated with an increased risk of later non-wrist fracture of up to one in five in the subsequent decade. 2. . According to the national guidelines in managing the fragility fractures of distal radius with regards the bone health review, we, as orthopedic surgeons, are responsible to detect the risky patients, refer them to the responsible team to perform the required investigations and offer the treatment. We reviewed our local database (E-trauma) all cases of fracture distal radius retrospectively during the period from 01/08/2019 to 29/09/2019. We included total of 45 patients who have been managed conservatively and followed up in fracture clinic. Our inclusion criteria was: women aged 65 years and over, men aged 75 years and over with risk factors, patients who are more than 50 years old and sustained low energy trauma whatever the sex is or any patient who has major risk factor (current or frequent recent use of oral or systemic glucocorticoids, untreated premature menopause or previous fragility fracture). We found that 96% of patients were 50 years old or more and 84% of the patients were females. 71% of patients were not referred to Osteoporosis clinic and 11% were already under the orthogeriatric care and 18% only were referred. Out of the 8 referred patients, 3 were referred on 1st appointment, 1 on the 3rd appointment, 1 on discharge from fracture clinic to GP again and 3 were without clear documentation of the time of referral. We concluded that we as trust are not compliant to the national guidelines with regards the osteoporosis review for the DRF as one of the first common presentations of fragility fractures. We also found that the reason for that is that there is no definitive clear pathway for the referral in our local guidelines. We recommended that the Osteoporosis clinic referral form needs to be available in the fracture clinic in an accessible place and needs to be filled by the doctor reviewing the patient in the fracture clinic in the 1st appointment. A liaison nurse also needs to ensure these forms have been filled and sent to the orthogeriatric team. Alternatively, we added a portal on our online database (e-trauma), therefore the patient who fulfils the criteria for bone health review should be referred to the orthogeriatric team to review

Venous Thromboembolism (VTE) prophylaxis is an essential part of orthopaedic surgeries in preventing life-threatening thromboembolic events such as Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). Orthopaedic surgery has the highest incidence rate of thromboembolic events as compared to any other surgical specialities, making it an essential component in managing any orthopaedic case. At Queen's Medical Centre (QMC), a major trauma centre in the United Kingdom (UK), sees up to 750 NOF fracture cases annually, making it one of the busiest trauma and orthopaedic centres in the UK. Our study aims to evaluate how VTE Prophylaxis is conducted in a UK Major Trauma Centre for NOF and pelvic fragility fractures and how human factors can improve its efficacy. The Nottingham University Hospitals (NUH) Trust has implemented new guidelines from August 2019 that patients with fragility fractures such as NOF and pelvic fractures are prescribed with 28 days VTE prophylaxis with Enoxaparin, or their own anti-coagulants if risk of thrombosis exceed the risk of bleeding. This is an adaptation from the trust to align their guidelines closer to the NICE 2018 guidelines. We will be evaluating the initial compliance of VTE Prophylaxis, identify and utilise human factors, then re-analyse the department after implementing interventions on the same batch of junior doctors working in the department. Data of 100 patients with fragility fractures were collected, 50 consecutive patients in the pre-intervention window during August 2019 and 50 in the post-intervention window during November 2019. The pre-intervention data had 43 NOF and 7 Pelvic fractures. Our study showed that 93% of NOF fracture and 100% of pelvic fracture received the correct course of VTE prophylaxis. The data was presented at the local department junior doctor academic session. Three simple human factor interventions were implemented over the course of September and October: Education to the trauma and orthopaedic department on the new guideline, extended VTE labels on drug charts for patients with fragility fractures, VTE reminder labels at doctors' stations. Another 50 consecutive patients' data were collected during November 2019. Data shows that 97.8% of NOF (p>0.05) and 60% of pelvic fracture (p>0.05) received the correct course of VTE prophylaxis. Our data has shown an increase in correct VTE prescription for NOF fracture patients, which is the main bulk of our fragility fracture patients whilst we see a drop in pelvic fracture patients. Due to the limited time frame of four months where junior doctors in the UK rotate between specialities, we are only able to collect data during the first month, implement interventions between datasets and collect data on the final month of the four-month rotation. A future bigger study might provide a more significant result on the department. We believe that the key to achieving 100% VTE prophylaxis in the T&O department is optimising human factors, educating junior doctors, who are not orthopaedic trained, with sufficient information of the guidelines, and evidence of the risk and benefits of providing prolonged VTE prophylaxis for orthopaedic patients. In conclusion, we found that QMC, a major trauma centre with high patient volume and turnover, has a high level of compliance with VTE prophylaxis for fragility fractures and it is imperative that utilising human factors will inch the department closer to its goal of 100% VTE compliance

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

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

We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age. Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts. Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency. Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers. These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis

It is known that Osteoporosis is the pathology of bone mass and tissue loss resulting in an increase of fragility, risk of fracture occurrence, and risk of fracture recurrence. We noted there was no definitive pathway in our last audit, therefore recommended: availability of the Osteoporosis clinic referral form in an accessible place, the form be filled by the doctor reviewing the patient in the first fracture clinic, and a liaison nurse to ensure these forms were filled and sent to the Osteoporosis clinic. This second audit analyses our Trust's response to these recommendations and effect achieved in Osteoporosis care. We reviewed our local data base from the 7/27/2020 – 10/2/2021 retrospectively for distal radius fractures who were seen in fracture clinic. We analysed a sample size of 59 patients, excluding patients who had already commenced bone protection medications. 67.7% of our patients had neither been on bone protection medications nor recorded referrals and 13.5% were already on bone protection medications when they sustained the fragility fracture. Ten out of the 51 patients were offered referral to the osteoporosis clinic, and one refused. This makes 20% (10 out of 50) of the patients had completed referrals. In comparison, in our first audit, 11% had already been on bone protection medications and 18% had completed referrals. The second cycle showed a slight increase in compliance. Majority of the referrals were completed by Orthopaedic Consultants in both audits and ana awareness increase noted among non-consultants in starting the referral process. Based on our analysis, our Trust has a slight improvement in commencing bone protection medications, associated with slight improvement in completing referrals to the Osteoporosis clinic. Despite our recommendations in the first audit, there is still no easily accessible definitive pathway to ensure our Trust's patients have timely access to bone protection and continued care at the Osteoporosis clinic. We recommend streamlining our recommendations to have a more effective approach in ensuring our Trust meets national guidelines. We will implement a Yes or No question assessment for patients visiting clinic in our electronic database which should assist in referral completions

Surgical treatment of fragility sacrum fractures with percutaneous sacroiliac (SI) screw fixation is associated with high failure rates in terms of screw loosening, cut-through and turn-out. The latter is a common cause for complications, being detected in up to 20% of the patients. The aim of this study was to develop a new screw-in-screw concept and prototype implant for fragility sacrum fracture fixation and test it biomechanically versus transsacral and SI screw fixations. Twenty-seven artificial pelves with discontinued symphysis and a vertical osteotomy in zone 1 after Denis were assigned to three groups (n = 9) for implantation of their right sites with either an SI screw, the new screw-in-screw implant, or a transsacral screw. All specimens were biomechanically tested to failure in upright position with the right ilium constrained. Validated setup and test protocol were used for complex axial and torsional loading, applied through the S1 vertebral body. Interfragmentary movements were captured via optical motion tracking. Screw motions in the bone were evaluated by means of triggered anteroposterior X-rays. Interfragmentary movements and implant motions in terms of pull-out, cut-through, tilt, and turn-out were significantly higher for SI screw fixation compared to both transsacral screw and screw-in-screw fixations. In addition, transsacral screw and screw-in-screw fixations revealed similar construct stability. Moreover, screw-in-screw fixation successfully prevented turn-out of the implant, that remained at 0° rotation around the nominal screw axis unexceptionally during testing. From biomechanical perspective, fragility sacrum fracture fixation with the new screw-in-screw implant prototype provides higher stability than with the use of one SI screw, being able to successfully prevent turn-out. Moreover, it combines the higher stability of transsacral screw fixation with the less risky operational procedure of SI screw fixation and can be considered as their alternative treatment option

Abstract. Objectives. Osteoporotic fractures tend to be more challenging than fractures in healthy bone and the efficacy of metal screw fixation decreases with decreasing bone mineral density making it more difficult for such screws to gain purchase. This leads to increased complication rates such as malunion, non-union and implant failure (1). Bioresorbable polymer devices have seen clinical success in fracture fixation and are a promising alternative for metallic devices but are rarely used in the osteoporotic population. To address this, we are developing a system that may allow osteoporotic patients to avail of bioresorbable devices (2) but it is important to establish if patients have any reservations about having a plastic resorbable device instead of a metal one. Therefore the aim of this study was to explore the acceptability of bioresorbable fracture fixation devices to people with osteoporosis. Methods. A cross sectional descriptive study was conducted in a UK wide population using convenience sampling. An online survey comprising nine survey questions and nine demographic questions was developed in Microsoft Teams and tested for face validity in a small pilot study (n=6). Following amendments and ethical approval, the survey was distributed by the Royal Osteoporosis Society on their website and social media platforms. People were invited to take part if they lived in the UK, were over 18 years old and had been diagnosed with osteoporosis. The survey was open for three weeks in May 2023. Responses were analysed using descriptive statistics. Results. There were 112 responses. Eight participants had not been diagnosed with osteoporosis and therefore did not meet the study criteria. Of the remaining 104, 102 were female and 2 were male and 102 were white (2 chose not to disclose their ethnicity). The majority of participants were aged 55–64 (34.6%) or 65–74 (37.5%), were college/university educated (38.5%) and had previously sustained a fragility fracture (52.9%). Only 3.9% of participants had heard of bioresorbable fracture fixation devices compared to 62.5% for metal devices. Most people were unsure if they would trust one type of device over the other (58.7%) and would ask for more information if their surgeon were to suggest using a bioresorbable device to fix their fracture (61.5%). The most commonly reported concerns were about device safety and efficacy: toxicity of the degradation products and the device breaking down too early before the fracture had healed. Two participants cited environmental concerns about increased use of plastics as a reason they would decline such a device. Conclusions. As expected, participants had little to no knowledge of bioresorbable polymer fixation devices. In general, they were willing to be guided by their surgeon but would require supporting information on the safety and efficacy of their long-term use. The results of this study show that it will be important to have relevant and understandable information to give patients when recommending these devices as treatments to ensure and support a shared-decision approach to patient care. 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

Cigarette smoking has a negative impact on the skeletal system by reducing bone mass and increasing the risk of fractures through its direct or indirect effects on bone remodeling. Recent evidence shows that smoking causes an imbalance in bone turnover, making bone vulnerable to osteoporosis and fragility fractures. In addition, cigarette smoking is known to have deleterious effects on fracture healing, as a positive correlation has been shown between the daily number of cigarettes smoked and years of exposure to smoking, although the underlying mechanisms are not fully understood. Smoking is also known to cause several medical and surgical complications responsible for longer hospital stays and a consequent increase in resource consumption. Smoking cessation is, therefore, highly advisable to prevent the onset of metabolic bone disease. However, some of the consequences appear to continue for decades. Based on this evidence, the aim of our work was to assess the impact of smoking on the skeletal system, particularly bone fractures, and to identify the pathophysiological mechanisms responsible for the impairment of fracture healing. Because smoking represents a major public health problem, understanding the association between cigarette smoking and the occurrence of bone disease is necessary in order to identify potential new targets for intervention

Introduction and Objective. Geriatric patients with a fragility fracture of the hip (FFH) are especially prone to sarcopenia with poor functional outcomes and quality of life. We assessed the prevalence of sarcopenia in older South African patients with FFH. Risk factors for sarcopenia were also investigated. Materials and Methods. From August 1 to November 30, 2018, all older patients with FFH were invited to participate. Sarcopenia was diagnosed based on the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Handgrip strength (HGS) and muscle strength were assessed. Muscle quantity was determined by dual-energy X-ray absorptiometry. Demographic information was collected, and 25-hydroxyvitamin D (25[OH]D) status was determined. Results. Of the 100 hip fracture cases, 65 were enrolled, and 52% (34/65) were sarcopenic (women: 62%; men: 38%). HGS accurately identified sarcopenia (sensitivity and specificity: 100%). Patients >80 years of age had a prevalence of sarcopenia twice (18/21 [83%]) that of younger patients (18/44 [36%]). Women with sarcopenia were smaller than those without (weight: p < 0.001; height: p < 0.001; body mass index: p¼0.018). Low 25(OH)D was almost universally present, with median 25(OH)D levels significantly lower in the patients with sarcopenia (27 nmol/L [interquartile range {IQR}: 20–39] vs. 40 nmol/L [IQR: 29–53]). Several risk factors, including advanced age; female sex; a smaller body size, especially among women; limited physical activity; and low 25(OH)D levels, were identified. Conclusions. The accuracy of HGS testing in this cohort underscores EWGSOP2's recommendation that muscle strength is key to sarcopenia. Further study and follow-up are required to determine the clinical relevance of sarcopenia among FFH patients. The prevalence of sarcopenia in our FFH population is high. Sarcopenia is associated with poor patient outcomes following surgical intervention. Orthopaedic surgeons should therefore be cognisant of the presentation and associated risk of sarcopenia as our patient populations age

Proximal humerus fractures are the third most common fragility fractures with treatment remaining challenging. Mechanical fixation failure rates of locked plating range up to 35%, with 80% of them being related to the screws perforating the glenohumeral joint. Secondary screw perforation is a complex and not yet fully understood process. Biomechanical testing and finite element (FE) analysis are expected to help understand the importance of various risk factors. Validated FE simulations could be used to predict perforation risk. This study aimed to (1) develop an experimental model for single screw perforation in the humeral head and (2) evaluate and compare the ability of bone density measures and FE simulations to predict the experimental findings. Screw perforation was investigated experimentally via quasi-static ramped compression testing of 20 cuboidal bone specimens at 1 mm/min. They were harvested from four fresh-frozen human cadaveric proximal humeri of elderly donors (aged 85 ± 5 years, f/m: 2/2), surrounded with cylindrical embedding and implanted with a single 3.5 mm locking screw (DePuy Synthes, Switzerland) centrally. Specimen-specific linear µFE (ParOSol, ETH Zurich) and nonlinear explicit µFE (Abaqus, SIMULIA, USA) models were generated at 38 µm and 76 µm voxel sizes, respectively, from pre- and post-implantation micro-Computed Tomography (µCT) images (vivaCT40, Scanco Medical, Switzerland). Bone volume (BV) around the screw and in front of the screw tip, and tip-to-joint distance (TJD) were evaluated on the µCT images. The µFE models and BV were used to predict the experimental force at the initial screw loosening and the maximum force until perforation. Initial screw loosening, indicated by the first peak of the load-displacement curve, occurred at a load of 64.7 ± 69.8 N (range: 10.2 – 298.8 N) and was best predicted by the linear µFE (R. 2. = 0.90), followed by BV around the screw (R. 2. = 0.87). Maximum load was 207.6 ± 107.7 N (range: 90.1 – 507.6 N) and the nonlinear µFE provided the best prediction (R. 2. = 0.93), followed by BV in front of the screw tip (R. 2. = 0.89). Further, the nonlinear µFE could better predict screw displacement at maximum force (R. 2. = 0.77) than TJD (R. 2. = 0.70). The predictions of non-linear µFE were quantitatively correct. Our results indicate that while density-based measures strongly correlate with screw perforation force, the predictions by the nonlinear explicit µFE models were even better and, most importantly, quantitatively correct. These models have high potential to be utilized for simulation of more realistic fixations involving multiple screws under various loading cases. Towards clinical applications, future studies should investigate if explicit FE models based on clinically available CT images could provide similar prediction accuracies

Objectives. Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Methods. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results. BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm. 2. vs 6.55/cm. 2. vs 5.25/cm. 2. ). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusion. BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP-induced microcrack accumulation may be significant. Cite this article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R. Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density. Bone Joint Res 2017;6:602–609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1

The international literature base demonstrates that individuals living with diabetes mellitus (DM) are at increased risk of mortality and post-operative complications following hip fracture surgery (HFS) than non-diabetics. Studies investigating databases in American, European or Asiatic populations highlight the impact geography can have on the resultant investigation. We aim to quantify the impact DM has on HFS patients in a single university hospital. The HIPE dataset of fragility fractures occurring in Galway University Hospital from 2014–2016 were analysed and cross referenced with hospital laboratory and public databases. A database of 759 individuals was created including 515 females and 237 males, with a mean age of 78+/−12.2 years, of which 110 patients had DM. The patient length-of-stay (PLOS) was comparable in all groups with patient age being the primary influencing factor. An extended PLOS correlated with an increased long-term mortality. A trend toward increased occurrence of sub-trochanteric fractures was observed in diabetics with fewer periprosthetic and intertrochanteric fractures. Patients with DM had a significant increased risk of post-operative mortality compared to non-diabetics. Males with DM where at a greater risk of death after HFS [HR 2.29, 95% CI 1.26–4.17. p=0.006] than females with DM [HR 1.69, 95% CI 0.99–2.91. p=0.056]. The presence of DM did not directly impact a patient's PLOS or increase the need for a re-operation. DM is associated with increased post-operative patient mortality and may influence the anatomical fracture pattern. This observation will support further investigation into the mechanical and biochemical changes occurring in the femur in individuals living with DM

Abstract. Objectives. Our objective was to determine the incidence of post-operative COVID-19 infection within the first two weeks following treatment at the COVID-free site. During the COVID-19 pandemic our hospital saw one of the highest rates of COVID-19 infection in the United Kingdom. As a result, our trauma services were relocated to a vacant private elective hospital to provide a ‘COVID-free’ setting for trauma patients. Patients admitted to the COVID-free site were screened for coronavirus infection and only treated at that site if asymptomatic. Those with symptoms were treated at the ‘COVID’ site. Method. We collected data at the COVID-free site during the first seven weeks of its’ establishment. Inclusion criteria were all patients presenting for operative management of limb trauma; however, fragility hip fractures were excluded. All patients were screened for symptoms of COVID-19 infection at their 2-week follow-up appointment. Results. 72 patients presented to our service during the study period. The mean age was 34.9 years (21 to 89). 62 patients had general anaesthesia (86%), 7 patients had regional anaesthesia (10%) and 3 patients had local anaesthesia (4%). One asymptotic patient who was swabbed for COVID-19 on admission returned a positive result. This patient had contracted the infection before surgery and was excluded from further analysis. 71 patients (100%) remained asymptomatic at follow-up and none had required medical attention for suspected COVID-19 infection. Conclusion. A ‘COVID-free’ trauma service was established in a private elective hospital during the pandemic. None of the patients undergoing urgent trauma surgery in this setting developed COVID-19 symptoms as a result of their hospital admission. Establishing a separate site with screening to avoid admission of patients with COVID-19 infection can allow safe emergency surgery. This data can support informed consent and reassure patients of their risks when we resume day case and elective surgery. 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

Background. Reduced bone mineral density is recognised as a risk factor for hip fractures and fragility fractures in general. Vitamin D is important in maintaining healthy bone mineral levels and can therefore affect risk of hip fracture. We investigated the correlation between vitamin D levels and bone mineral density, as well as fracture type, in neck of femur fractures and also assessed the relationship of vitamin D and social deprivation. Method. We included all patients admitted to our department, with a neck of femur fracture over one year (October 2013 to October 2014). We analysed vitamin D levels for all patients during admission and compared these to bone mineral density scores, based on DEXA scan results; hip fracture type & comminution, based on admission radiographs; and levels of social deprivation, based on the patient's address. Results. In total 360 patients were admitted over the study period, with a neck of femur fracture, of which 298 had vitamin D assessed and 76 had DEXA scans. Of these cohorts, 71% were found to be vitamin D deficient and 7% had osteoporosis. No significant correlation was found between vitamin D scores and bone density, or with level of vitamin D deficiency and fracture type or comminution. A significant correlation was however identified, between low vitamin D levels and decreasing levels of social deprivation (R=0.11, p=0.04). Conclusion. No relationship was identified between vitamin D levels and hip fracture type, suggesting that vitamin D cannot be used to predict patients at risk of more comminuted fractures. Although no relationship was also identified for bone mineral density and vitamin D, this may be because the sample size of DEXA scans was relatively small. Interestingly the relationship between vitamin D and social deprivation was the reverse of what was expected and suggests that affluent individuals may be at greater risk of low vitamin D

There is increasing interest in using anabolic factors such as stem cells to augment fragility fracture repair. One of the factors associated with fracture healing is the retention and migration of stem cells to the site of injury (1–3). The aim of this study was to isolate stem cells from osteopenic rats and investigate and compare the CD marker expression, proliferation, migration, osteogenic and adipogenic differentiation. The hypothesis of this study is that the migration of MSCs from young, adult and ovariectomised (OVX) rats will have different proliferation, differentiation and migratory abilities. CD marker expression of MSCs from young, adult and osteopenic rats was measured using flow cytometry. Proliferation, osteogenic differentiation and adipogenic differentiation was measured using Alamar Blue, ALP expression and Alizari n Red and quantitative Oil red O respectively. Cells were incubated in Boyden chambers to quantify their migration towards SDF1. Data was analysed using a Student t-test where p values < 0.05 were considered significant. MSCs from all 3 groups of rats had similar proliferation and expression of CD29(>90%), CD90(>96%), CD34(<5%) and CD45(approx 10%). The proliferation rate was also similar. However, interestingly the migration and differentiation ability was significantly different between the MSCs from the 3 groups of rats. The young MSCs were not only better at differentiating into bone and fat, but they also migrated significantly more towards SDF1. MSCs from OVX rats are similar to MSCs from young rats. However when induced to turn into bone, fat and migrate towards SDF1, young MSCs are significantly more responsive than MSCs from OVX and adult control rats. The poor homing ability and differentiation of the stem cells and their retention may result in a reduction in bone formation leading to delayed union in fractures of osteoporotic patients(4)

Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity . 1,2,3. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Up-regulation of specific microRNAs has been identified in-vivo in osteoporotic patients . 4,5. It is hypothesized that modulation of specific microRNA expression may have a key role in future targeted therapies of musculoskeletal diseases. The assessment and analysis of their potential therapeutic use in Osteoporosis is of great importance, due to the burden of the disease. We have developed a 3D osteoporotic model from human bone marrow, without the use of scaffold. Magnetic nanoparticles are utilised to form spheroids, which provides a closer representation of the in-vivo environment than monolayer culture. This model will provide the basis for analysing future microRNA experiments to assess the potential up-regulation of osteoblastogenesis without cessation of osteoclast activity. The results of initial monolayer and spheroid experiments will be presented. Optimisation of the osteoporotic bone marrow culture conditions, involving response to differentiation medias, analysis of adipose and bone markers and cell migration in spheroid culture will be displayed. Quantitative and qualitative results, including fluorescence microscopy and in cell western, assessing the monolayer and spheroid cultures will be presented. The development of a pseudo osteoporosis model from healthy bone marrow will also be discussed. This model will form a basis of future work on microRNA targeting. The development of improved therapies for osteoporosis is of great significance due to the predicted rise in incidence of the disease and associated fragility fractures. Targeted therapies, such as the manipulation of microRNA expression, offer the opportunity to increase osteoblastogenesis and decrease osteoclastogenesis, potentially without the associated side effects of older, systemic therapies. We believe our 3D human bone marrow derived osteoporotic model offers the closest relation to the in-vivo environment for assessment and manipulation of microRNA expression

The pathogenesis of falling bone mineral density (BMD) as a universal feature of advancing age is poorly understood. 1. Frequently culminating in the development of osteoporosis, the process is attributable to more than 500,000 fragility fractures occurring every year in the UK Such injuries are associated with great levels of morbidity, mortality and a £3.5 billion cost to the healthcare economy. 2. . With age, humans are known to accumulate somatic mitochondrial DNA (mtDNA) mutations in mitotic and post mitotic tissue, and stem cell precursors. 3. Compelling evidence in recent years, particularly that provided by animal models suggests that these mutations are intrinsic to the ageing process. 4–6. We provide evidence for the first time that mitochondrial dysfunction contributes significantly to the failure of bone homeostasis and falling BMD. We have utilised a mouse model that accumulates mtDNA mutations at 3–5 times the rate of normal mice, consequently ageing and developing osteoporosis prematurely. 7. , to clearly demonstrate that osteoblasts are vulnerable to mtDNA mutations. We have developed a new quadruple immunofluorescent assay to show that mitochondrial respiratory chain dysfunction occurs in osteoblasts as a consequence (p < 0.0001). We show that this mitochondrial dysfunction is associated with reduced BMD in female and male mice by 7 (p = 0.003) and 11 (p = 0.0003) months of age respectively. Using osteoblasts derived from mesenchymal stem cells extracted from male and female mice with mitochondrial dysfunction aged 4, 7 and 11 months, we demonstrate a vastly reduced capacity to produce new mineralised bone in vitro when compared to wild type cell lines (p < 0.0001). Exercise was found to have no beneficial effect on osteoblast and whole bone phenotype in this mouse model. It is likely that mtDNA mutations accumulating over a longer time period in human ageing have significantly detrimental effects on bone biology and diminishing BMD

Fragility fractures are an increasing cause of morbidity and mortality in the elderly population. Their association with reduced bone mineral density (BMD) is well documented. It is a reasonable assumption that hip fracture severity is linked to the magnitude of bone loss, (the lower the BMD, the more severe the fracture), however it is not known whether this correlation exists. Our aim therefore was to investigate the relationship between BMD and hip fracture severity. We reviewed 142 patients, 96 females and 46 males, mean age 74 years (49-92), who had sustained a hip fracture following a simple ground level fall. All had subsequently undergone DEXA bone scanning of the contralateral hip and lumbar spine. Fractures were classified as intra-capsular, extra-capsular or subtrochanteric, then sub-classified using the Garden, Jensen and Seinsheimer classifications respectively. They were grouped into simple (stable) or comminuted (unstable) fracture patterns. Risk factors for osteoporosis were recorded. A low hip BMD (<2.5) was associated with an increased risk of extra-capsular fracture (p=0.025). However, no association with fracture type (extra vs. intra-capsular, p>0.05) was identified with the following variables; age, gender, BMI <25, smoking, and excess alcohol intake. We did not find any statistically significant associations between fracture severity and the nine principle variables tested for: age; gender; smoking; BMI < 25; alcohol excess and low hip or lumbar BMD T or Z score <-2.5. Although the association between BMD and risk of fragility fractures is well documented, the results of this study would suggest that severity of hip fractures does not follow this correlation. Therefore, no assumption can be made about BMD of the proximal femur based on the severity of fracture observed on plain radiographs alone