Aging impairs the regenerative capacity of musculoskeletal tissues and is associated with poor healing outcomes. PolgA. D257A/D257A. (PolgA) mice present a premature aging phenotype due to the accumulation of mitochondrial DNA (mtDNA) point mutations at rates 3 – 5 fold higher compared to wild type mice. Consequently, PolgA mice exhibit the premature onset of clinically-relevant musculoskeletal aging characteristics including frailty, osteo-sarcopenia, and kyphosis. I will present our recent findings on the use of PolgA mice to investigate the effects of aging on the regenerative capacity of bone. In particular, I will focus on the mechano-sensitivity of the regenerative process in aged bone environments and the opportunities it presents for clinical translation of mechanical intervention therapies

Introduction and Objective. Scaphoid waist fractures (SWF) are notable in upper limb trauma and predominantly occur in young men. Morbidities associated with SWF include fracture non-union, premature arthritis and humpback deformity. Delayed treatment and non-adherence to fracture immobilisation increases likelihood of these complications. There is evidence that men engage in negative health behaviours such as delayed help-seeking. The Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) conducted interviews in individuals who had sustained a SWF. Although SWIFFT showed multiple social determinants for the overall injury and healing experience, a key factor this novel study considers is age and sex. This study aimed to analyse interview data from young male participants in SWIFFT to help distinguish the experience of SWF in young men, through exploring the influence of masculinity. Materials and Methods. A purposive sample of 12 young male participants were selected from SWIFFT. These participants were enrolled from a possibility of 13 different centres across Britain. There were 17 semi-structured interviews produced from these participants, and this was thought to be sufficient for data saturation. These interviews were evaluated through deductive thematic analysis with an open-coding approach, with respondents’ experiences being compared against themes documented in men's health literature. The “Braun and Clarke (2006) Six Phases of Thematic Analysis” methodology was adopted to perform this. Results. There were three thematic models developed in the data set, which then were further divided into subthemes. Model 1: Negative Health Behaviour Prior to Treatment, model 2: Feeling Frail and model 3: Need for Speed. Model 1 corroborated that participants were inclined to sustain the injury as a result of risk-taking and would subsequently hesitate to seek treatment. Model 2 indicated that as a result of the injury, respondents were unable to engage in physical activities and activities of daily living. Respondents exercised caution to varying extents after sustaining a SWF. Model 3 highlighted that interviewees were prone to non-adherence with fracture immobilisation and in hindsight resumed employment prematurely. Conclusions. The findings of this study demonstrate that masculinity is significantly influential on the experience of SWF in young men. This was indicated through the results of thematic analysis strongly corresponding with behaviours established in men's health literature. Educational interventions could be of value in addressing behaviours observed in this population group, such as delayed help-seeking and non-compliance with fracture immobilisation. Further work in patient education and concordance with treatment after sustaining a SWF may be beneficial to longer term outcomes. In turn, this may reduce complications associated with SWF in young men

Acetabular morphology and orientation differs from ethnic group to another. Thus, investigating the natural history of the parameters that are used to assess both was a matter of essence. Nevertheless, clarification the picture of normal value in our society was the main aim of this study. However, Acetabular head index (AHI) and center edge angle (CEA) were the most sensitive indicative parameters for acetabular dysplasia. Hence, they were the main variables used in evaluation of acetabular development. A cross-sectional retrospective study that had been done in a tertiary center. Computed tomography abdomen scouts’ radiographs of non-orthopedics patients were included. They had no history of pelvic or hips’ related symptoms or fractures in femur or pelvis. Images’ reports were reviewed to exclude those with tumors in the femur or pelvic bones. A total of 81 patients was included with 51% of them were males. The mean of age was 10.38± 3.96. CEA was measured using Wiberg technique, means of CEA were 33.71±6.53 and 36.50±7.39 for males and females, respectively. Nonetheless, AHI means were 83.81±6.10 and 84.66±4.17 for males and females, respectively. On the other hand, CEA was increasing by a factor 0.26 for each year (3-18, range). In addition, positive significant correlation was detected between CEA and age as found by linear regression r 2 0.460 (f(df1,79) =21.232, P ≤0.0001). Also, Body mass index (BMI) was positively correlated with CEA r 0.410, P 0.004). This study shows that obesity and aging are linked to increased CEA. Each ethnic group has its own normal values that must be studied to avoid premature diagnosis

Although bone morphogenetic protein 2 (BMP-2) has been FDA-approved for spinal fusion for decades, its disadvantages of promoting osteoclast-based bone resorption and suboptimal carrier (absorbable collagen sponge) leading to premature release of the protein limit its clinical applications. Our recent study showed an excellent effect on bone regeneration when BMP-2 and zoledronic acid (ZA) were co-delivered based on a calcium sulphate/hydroxyapatite (CaS/HA) scaffold in a rat critical-size femoral defect model. Therefore, the aim of this study was to evaluate whether local application of BMP-2 and ZA released from a CaS/HA scaffold is favorable for spinal fusion. We hypothesized that CaS/HA mediated controlled co-delivery of rhBMP-2 and ZA could show an improved effect in spinal fusion over BMP-2 alone. 120, 8-week-old male Wistar rats (protocol no. 25-5131/474/38) were randomly divided into six groups in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA). A posterolateral spinal fusion at L4 to L5 was performed bilaterally by implanting group-dependent scaffolds. At 3 weeks and 6 weeks, 10 animals per group were euthanized for µCT, histological staining, or mechanical testing. µCT and histological results showed that the CaS/HA + BMP-2 + local ZA group significantly promoted bone regeneration than other treated groups. Biomechanical testing showed breaking force in CaS/HA + BMP + local ZA group was significantly higher than other groups at 6 weeks. In conclusion, the CaS/HA-based biomaterial functionalized with bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant spinal fusion outcome. Acknowledgements: Many thanks to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology)

Introduction. Osteoarthritis (OA) often results from joint misloading, which affects chondrocyte calcium signaling through mechano-sensitive receptors such as Piezo1, -2, and TRPV4. Activation of Piezo1, especially under inflammatory conditions, can trigger premature chondrocyte apoptosis. Intra-articular glucocorticoid therapy, while beneficial against inflammation and pain in osteoarthritis, may induce oxidative stress and chondrotoxicity at higher doses. This study aims to assess the effects of glucocorticoids, particularly triamcinolone, on chondrocyte elasticity and mechanosignaling. Method. Chondrocytes isolated from articular condyles obtained from patients undergoing knee replacement surgery (n= 5) were cultured for 7 days in triamcinolone acetonide (TA) at different concentrations (0.2µM – 2mM). Cytoskeletal changes were assessed by F-actin labeling. Cell elasticity was measured using atomic force microscopy (AFM). Labeling cells (n=6 patients) with the calcium-sensitive dye (Fluo-4) enabled monitoring changes in intracellular calcium fluorescence intensity during guided single-cell mechanical indentation (500 nN) by AFM. Result. Cell exposure to 2 mM TA led to cell death and crystallization of TA in the cell culture media. However, the concentration of TA for intra-articular application is 46 times higher at 92.1 mM (40 mg/ml). The maximal pharmacological effect on viable cells was observed at 0.2 mM. AFM results showed a significant decrease of elasticity (p<0.001), alongside significantly higher calcium intensities both prior to and during mechanical stimulation in the TA-treated samples (p<0.05). Conclusion. Administration of TA significantly impacts the mechanical properties of chondrocytes, reducing cellular elasticity while simultaneously enhancing calcium-dependent mechanosensitivity. This data suggests a correlation between glucocorticoid-induced changes in cell elasticity and cell mechanosensitivity. Finding ways to minimize the effect of glucocorticoids on cell mechanosensitivity could help to make future therapies safer and reduce side effects

Introduction. Selective screening of children at risk for developmental dysplasia of the hip (DDH) is based on clinical examination and risk factor identification. Two meta-analyses published in 2012 found breech presentation, family history of DDH, female sex and primiparity to increase the risk of DDH. However, the DDH definition, reference tests and age of the examined children vary considerably, complicating the translation of those findings to current screening guidelines. The aim of this meta-analysis was to evaluate the association of previously proposed risk factors to the risk of sonographically verified DDH. Method. We searched PubMed, EMBASE and Cochrane library to identify cohort, RCTs, case-control and cross-sectional studies from 1980 to 2023 in English language. Eligible studies included participants under three months of age, where the diagnosis of DDH was made by hip ultrasound using the gold standard Graf method and reported information on one or more of the proposed risk factors and final diagnosis was available. Result. Of 5363 studies screened, 20 studies (n=64543 children) were included. Breech presentation (OR: 4.2, 95%CI 2.6-6.6), family history (3.8, 95%CI 2.1-7.2), female sex (2.5, 95%CI 1.7-3.6), oligohydramnios (3.8, 95%CI 1.7-8.5) and high birthweight (2.0, 95%CI 1.6-2.5) significantly increased the risk of DDH. C-section, primiparity, multiple births, low birthweight and prematurity were not found to increase the risk for DDH, and there was only one study about clubfoot as a risk factor. Heterogeneity was high (I. 2. >75%) in all the tested factors except high birthweight (I. 2. =0%). Subgroup analysis was performed to investigate these heterogeneities. Conclusion. Family history of DDH and breech presentation are associated with significant increase of the risk of sonographic DDH in children aged three months. A similar risk increase was detected for oligohydramnios, which was not detected in previous meta-analyses. Additionally, the DDH risk increase of female sex was found to be lower than previously reported

Introduction. Osteoporosis accounts for a major risk factor of fracture-associated disability or premature death in the elderly. Enhancement of bone anabolism for slowing osteoporosis is highly demanding. Exerkine fibronectin type III domain containing 5 (FNDC5) regulates energy metabolism, inflammation, and aging. This study was aimed to investigate whether Fndc5 signaling in osteoblasts changed estrogen deficiency-mediated bone loss or microarchitecture deterioration. Method. Female osteoblast-specific Fndc5 transgenic mice (Fndc5Tg), which overexpressed Fndc5 under the control of key osteoblast marker osteocalcin promoter, were given bilateral ovariectomy to induce estrogen deficiency-mediated osteoporosis. Bone mass, microstructures, and biomechanical properties were quantified using μCT imaging and material testing. Dynamic bone formation was traced using fluorescence calcein. Osteogenic differentiation and adipocyte formation of bone-marrow mesenchymal cells were investigated using von Kossa staining and Nile red staining, respectively. Serum osteocalcin, CTX-1 and TRAP5b levels were quantified using designated ELISA kits. Mitochondrial respiration was investigated using Seahorse Extracellular Flux Analyzer. Result. Fndc5Tg mice developed relatively higher bone mass and microarchitecture than wild-type mice. Fndc5 overexpression attenuated the losses of bone mineral density and trabecular network, including trabecular volume, thickness, and trabecular number, and improved cortical thickness and porosity in ovariectomized mice. Gain of Fndc5 function preserved biomechanical characteristics (maximum load, breaking force, and energy), serum bone formation marker osteocalcin levels, and bone formation rate, whereas it reduced serum bone resorption makers CTX-1 and TRAP5b levels, osteoclast overburden, and marrow adiposis. In vitro, Fndc5 reversed the estrogen deficiency-mediated mineralized matrix underproduction and adipocyte formation of bone-marrow mesenchymal cells, and inhibited osteoclast formation in osteoporotic bone. Mechanistically, Fndc5 activated AMPK signaling, promoting mitochondrial respiration and ATP production to enhance osteoblastic activity. Conclusion. Fndc5 signaling exerted bone-protective actions delaying estrogen deficiency-mediated osteoporosis. This study highlighted a new molecular remedial option for osteoporosis development by manipulating Fndc5 functions

The use of retrograde femoral intramedullary nails in children for deformity correction is controversial. It is unknown if the injury to the central part of the growth plate results in premature bony union, leading to limb deformities or discrepancies. The aim of this study was to assess physeal healing and bone growth after insertion of a retrograde femoral nail thorough the centre of the physis in a skeletally immature experimental porcine model. Eleven immature pigs were included in the study. One leg was randomised for operation with a retrograde femoral nail (diameter 10.7 mm), whilst the non-operated contralateral remained as control. All nails were inserted centrally in coronal and sagittal plane under fluoroscopic guidance, and the nails spanned the physis. The nails were removed at 8 weeks. Both femora in all animals underwent MRI at baseline (pre-operatively), 8 weeks (after nail removal) and 16 weeks (before euthanasia). Femoral bone length was measured at 5 sites (anterior, posterior, central, lateral and medial) using 3d T1-weighted MRI. Growth was calculated after 8 weeks (growth with nail) and 16 weeks (growth without nail). Physeal cross-sectional area and percentage violated by the nail was determined on MRI. Operated side was compared to non-operated. Corresponding 95% confidence intervals were calculated. No differences in axial growth were observed between operated and non-operated sides. Mean growth difference was 0,61 mm [−0,78;2,01] whilst the nail was inserted into the bone and 0,72 mm [−1,04;1,65] after nail removal. No signs of angular bone deformities were found when comparing operated side to non-operated side. No premature bony healing at the physis occurred. Histology confirmed fibrous healing. Mean physeal violation was 5.72% [5.51; 5.93] by the femoral nail. The insertion of a retrograde femoral nail through the centre of an open physis might be a safe procedure with no subsequent growth arrest. However, experiments assessing the long term physeal healing and growth are needed

Mitochondrial dysfunction has been demonstrated in aging and osteoarthritic tissues. We investigated knee joints of prematurely aging mitochondrial DNA mutator mice (PolgD275A) to evaluate a relationship between mitochondrial dysfunction and osteoarthritis. Cartilage damage was evaluated using OARSI histopathology grading and osteoclast numbers were quantified by tartrate-resistant acid phosphatase staining in wild type, heterozygous and homozygous PolgD275A mice. Subchondral cortical plate and epiphyseal trabecular bone structures were determined by micro-computed tomography. Apoptosis in cartilage and subchondral bone tissues was studied using an indirect TUNEL method. Homozygous mutants displayed osteopenia of the epiphyseal trabecular bone and subchondral cortical plate in comparison to wild type and heterozygous mutants. Subchondral osteopenia was associated with a strong increase of osteoclast numbers (0.88±0.30/mm bone perimeter) compared to heterozygous (0.25±0.03/mm) and wild type mice (0.12±0.04/mm). Wild type mice as well as hetero- and homozygous mutants displayed low-grade cartilage degeneration due to loss of cartilage proteoglycans. In contrast, chondrocyte hypertrophy was more abundant in the homozygous mice. There were no differences in chondrocyte apoptosis rates between groups. Prematurely ageing mtDNA mutator mice with or without further mechanic or metabolic stimuli might serve as a valuable model for further experimental studies on aging-induced osteoporotic OA phenotype

Abstract. Objective. To assess the prevalence of acetabular retroversion in patients presenting with Slipped Upper Femoral Epiphysis using both validated radiological signs and CT-angle measurements. Methods. A retrospective review of all cases involving surgical management for acute SUFE presenting to the Royal Children's Hospital, Melbourne were assessed from 2012–2018. Pre-operative plain radiographs were assessed for slip angle, validated radiological signs of retroversion (post wall/crossover/ischial spine sign) and standardised post-operative CT Scans were used to assess cranial and mid-acetabular version. Results. 116 SUFEs presented in 107 patients who underwent surgical intervention; 47 females and 60 boys, with an average age of 12.7 years (range 7.5–16.6 years). Complete radiological data was available for 91 patients (99 hips) with adequate axial CT imaging of both hips. 82% patients underwent pinning in situ (PIS) with subcapital realignment surgery (SRS) performed in 18% (slip angles >75°). Contralateral prophylactic hip PIS was performed in 72 patients (87%). On the slip side, 68% of patients had 1 or more radiological signs of retroversion in the slipped hip, with 60% on the contralateral side. The mean cranial and mid-acetabular version measurements were −8°(range −30 – 8°) and 10.5°(range −10 – 25°), respectively. Conclusions. Acetabular retroversion is rare in the normal population with studies reports ranging from 0–7%. This study showed an increased prevalence of 68% in SUFE patients, which is likely to be a primary anatomical abnormality, subsequently increasing the shear forces across the proximal femoral growth plate due to superior over-coverage. The resulting CAM lesion from SUFE in combination with the pincer lesion due to retroversion can lead to premature hip impingement and degeneration. Further larger studies are required to assess if acetabular retroversion is a true risk factor, and its role in helping guide management including prophylactic pinning. 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. The doses of local rhBMP-2 in commercially available materials are high with known drawbacks such as inflammation and premature bone resorption. The latter can be prevented by adding bisphosphonates like zoledronic acid (ZA) but systemic ZA has side effects and patient adherence to treatment is low. In a recent study, we have shown that local co-delivery of rhBMP-2 and ZA via a calcium sulphate/hydroxyapatite (CS-HA) biomaterial can be used to regenerate both cortical and trabecular bone in a rat model of metaphyseal bone defect. Even low doses of local ZA in the biomaterial showed promising results and increased bone formation within the defect compared to the controls. A step before clinical translation of the local treatment regimen is to evaluate the in-vivo release kinetics of these additives and thus in this study, we aimed to investigate the in-vivo pharmacokinetics of rhBMP-2 and ZA from the CS-HA biomaterial in a rat abdominal muscle pouch model over a period of 4-weeks. Methods. In-vivo release kinetics of 125I labeled rhBMP-2 and 14C labeled ZA was performed using an abdominal muscle pouch model in rats (n=6). Both rhBMP-2 and ZA were labeled commercially with a radiochemical purity of >95%. The detection of 125I -rhBMP-2 release was performed by implanting pellets of the CS-HA biomaterial containing 125I -rhBMP-2 and ZA and the same animals followed over a period of 4-weeks (day 1, 3, 7, 14, 21& 28) using SPECT imaging. Similarly, the 14C-ZA was detected by implanting CS-HA pellets containing rhBMP-2 and 14C-ZA. Release was detected via scintillation counting and at each time point (Day 1, 7, 14& 28) 6-animals were sacrificed. Results. BMP Release. The CS-HA biomaterial retained 95±11% after 3-days, 88±12% after a week, 66±9% after 2 weeks, 51±5% after 3 weeks and 43±7% of 125I labeled rhBMP-2 after 4-weeks in-vivo (SPECT-CT). ZA Release. The CS-HA biomaterial retained 89±14% after a week, 84±8% after 2 weeks, 83±9% after 3 weeks and 77±3% of 14C labeled ZA after 4 weeks of in-vivo implantation. Discussion. Improved carriers and better knowledge of the release might improve the effect of bone active drugs in orthopedics. Our previous study shows that an off-the-shelf ceramic biomaterial combined with ZA alone or with both rhBMP-2 and ZA can be used to regenerate bone with potential for clinical translational. This study demonstrates long-term co-delivery of both rhBMP-2 and ZA in-vivo via the biomaterial. Constant availability of rhBMP-2 over a long period of time can give osteoinductive properties to the material while presence of local ZA prevents premature bone loss. The pharmacokinetic release pattern differs from what we have reported in vitro with less BMP and more ZA being released in vivo during the first 4 weeks. We speculate that rapid protein passivation of the ceramic material slows the release of BMP and partly preventing the ZA binding to apatite

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

Background. Innovative developments for total knee arthroplasty enhanced anatomical design and fixation in order to decrease particle-induced aseptic implant loosening. As hypersensitivity reactions to metallic implant materials have been recognized to possibly cause premature implant failure, ceramic materials might constitute a proper alternative solution. The aim of this prospective short-term study was the initial comparison of a completely metal-free ceramic with a geometrically identical metallic arthroplasty over a one-year follow-up period. Methods. Eighty patients requiring primary total knee arthroplasty were enrolled within this open-label prospective comparative study. Patients were randomly divided among two groups to either undergo implantation of a completely metal-free system using a composite matrix material containing aluminum oxide (Al2O3) and zirconium oxide (ZrO2) (n=40), or an anatomically identical metallic knee system made of a cobalt-chromium alloy (Co28Cr6Mo) (n=40) produced by the same manufacturer. Clinical assessment was performed preoperatively, and during follow-up at three and twelve months using the Knee Society Score, Oxford Knee Score and EQ-5D-VAS. For radiological evaluation, standard preoperative and postoperative standardized radiographs were taken at mentioned follow-up visits. Results. Demographical data were not significantly different among our two study groups, and no patient has been lost to follow-up. The postoperative clinical scores improved significantly at three and twelve month follow-ups, but did not differ statistically among groups. The radiologically evaluated mean postoperative mechanical and anatomical axes showed proper alignment within both groups at all times. Notably, no revision surgery had to be performed, and no complications were recorded whatsoever. Conclusion. To our knowledge, this is the first study comparing a total ceramic metal-free knee system with a geometrically identical metallic TKR. Within the short-term follow-up of minimally one year, no significant differences could be demonstrated clinically or radiologically, therefore making this ceramic knee system a suitable option for patients with a known hypersensitivity to metal. Mid-term and long-term studies will be required to demonstrate the overall efficiency of this TKR to potentially expand its medical indication

The screw fastening torque applied during bone fracture fixation has a decisive influence on subsequent bone healing. Insufficient screw tightness can result in device/construct instability; conversely, excessive torques risk damaging the bone causing premature fixation failure. This effect is even more prominent in osteoporotic bone, a condition associated annually with almost 9 million fractures worldwide. During fracture fixation, screw tightening torque is applied using subjective feel. This approach may not be optimal for patient”s recovery, increasing risk of fixation failure, particularly in osteoporotic bone, and potentially require revision surgical interventions. Besides bone density, various factors influence the performance of screw fixation. These factors include bone geometry, cortical thickness and time-dependant relaxation behaviour of the bone. If the influence of screw fastening torque on the bone and relationships between these factors was better understood, the surgical technique could be optimised to reduce the risk of complications. Within this study, we developed an axisymmetric finite element (FE) model of bone screw tightening incorporating viscoelastic behaviour of the cortical bone such as creep and stress relaxation. The model anticipated time-dependent behaviour of the bone for different bone thickness and density after a typical bone fixation screw had been inserted. The idealised model has been developed based on CT scans of bones with varying densities and inserted screws. The model was validated through a series of experiments involving bovine tibiae (4–5 months) to evaluate the evolution of surface strains with time (Ncorr v1.2). Stress distribution was assessed in photoelastic experiments using acrylic analogues. Relaxation tests have been performed in aqueous environment for up to 48 hours to ensure the relaxation would be complete. The creep behaviour (maximum principal strain) was compared against computational predictions. Our early simulations predicted relaxation strains on the surface of the bone to be 1.1% within 24 hours comparing favourably to 1.3% measured experimentally. Stress distribution patterns were in agreement with photoelastic results. Using experimentally derived viscoelastic properties, the model has the potential to predict creep and stress relaxation patterns after screw insertion with different fastening torques for bones with varying density and geometry. We aim to develop this into a planning tool providing guidance to surgeons for optimal tightening when using screw fixation, particularly in reduced quality bone

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

When performing total knee replacement (TKR), surgeons must select a size of tibial component tray that most closely matches the anatomy of the proximal tibia. As implants are available in a limited range of sizes, it may be necessary to slightly under or oversize the component. There are concerns overhang could lead to pain from irritation of soft tissues, and underhang could lead to subsidence and failure. 154 TKRs at 1- or 5-year follow up were reviewed prospectively. Oxford Knee Score (OKS), WOMAC and SF-12 was recorded along with pain scores. Scaled radiographs were reviewed and grouped into perfect sizing (78 TKRs, 50.6%), underhang in isolation (48 TKRs, 31.1%), minor overhang 1–3 mm (10 TKRs, 6.49%) or major overhang >3 mm (18 TKRs, 11.7%). There was no significant difference in the SF-12 (p=0.356), post-operative OKS (p=0.401) or WOMAC (p=0.466) score. For the OKS, there was no difference for the scores collected at 1 year (p=0.176) or at 5 years (p=0.883). Pre-operative OKS was well matched between the groups (p=0.152). There was no significant difference in the improvement in OKS from pre-operative scores (p=0.662). There was no significant difference in either the OKS or WOMAC pain scores (p=0.237 and 0.542 respectively). There was no significant association of medial overhang with?medial knee pain (p=1.000) or lateral overhang with lateral knee pain (p=0.569) when compared to the group of patients with a well sized tibial component. Our results suggest that tibial component overhang or underhang has no detrimental affect on outcome or pain scores. Surgeons should continue to select the tibial component that most closely fits the rim of the proximal tibia while accepting slight overhang if necessary due to the potential longer-term complications of subsidence and premature failure with an undersized tibial tray

Summary Statement. The implantation of scaffold-free CTE from suspension culture into growth-plate defects resulted in a significant reduction in growth arrest of the rabbit tibia. Introduction. In childhood and adolescence, the growth plate injury can cause partial premature arrest of growth plate, which can make problems such as leg length discrepancy and angular deformity. Bone bridge resection and variable implantation materials such as fat, bone wax, silastic and craniopalst has been investigated. However, those procedures may show limitations including the control of bone growth and long term safety of implant materials in vivo. As an alternative, homogeneous or heterogeneous cartilage cells and stem cell transplants have been tried. In this method, scaffold for cell transplantation is needed. But, so far the most suitable scaffold has not been established. Recently, some authors generated a cartilage tissue equivalent (CTE) using a suspension culture with biophysical properties similar to native hyaline cartilage. Therefore we are able to transplant the CTE without scaffold to the physeal defect. The purpose of this study was to investigated the effects of a transplantation of a vitro-generated scaffold-free tissue-engineered cartilage tissue equivalent (CTE) using a suspension chondrocyte culture in a rabbit growth arrest model. Material and Method. Cartilage tissue equivalent culture. The CTE was generated by the suspension culture of chondrocytes (2 × 10. 7. /well/1 mL) which was isolated from articular cartilage of 5 weeks New Zealand white rabbit on a 24-well plate (2.4 cm. 2. /well) treated with poly HEMA (nunc, Roskide, Denmark) for up to 8 and 16 weeks. (2)Partial growth arrest animal model. An experimental model for growth arrest was created by excising the growth plate at the proximal medial side of tibia with the 4 mm in diameter and 4 mm in depth from 6-week-old New Zealand white rabbits. Two experimental groups were set to evaluate CTE implantation; group I, no implantation as controls; group II, implantation of CTE. (3) Evaluation of effect of the transplantation of CTE. Serial plain radiographs were performed at one week. The medial proximal tibial angle (MPTA) was measured for assessing the degree of angular deformity. Histologic examination using HE stain, Alcian bule and immunohistochemistry was done at 4 and 8 weeks after surgery. Results. Radiographic results: In group I, all damaged growth plates were arrested and angular deformities appeared 4 weeks later. In groups II, angular deformities were much less than in the control group. Histologic result: In group I, bone bridge formation was shown at the damaged growth plate at 4 weeks after surgery. In group II, regeneration of growth plates was recognised at 4 and 8 week after surgery. However, the thickness of regenerated growth plate at 8 weeks specimen was thinner than that of 4 weeks specimen. Discussion and Conclusion. The implantation of scaffold-free CTE from suspension culture into growth-plate defects resulted in a significant reduction in growth arrest of the rabbit tibia

Summary. Application of RSA in supine and standing positions allows pelvic fracture stability to be measured more accurately than current techniques. RSA may enable a better understanding of these injuries. Introduction. The in vivo stability of the pelvic ring after fracture stabilisation remains unknown. Plain radiographs have a low accuracy in diagnosing loss of fracture reduction over time. Radiostereometric analysis (RSA) is an accurate imaging measurement method that has previously been applied to measure the healing of other fractures. This pilot study investigated the potential application of RSA in supine and standing positions to measure pelvic fracture stability over time and under weightbearing load. Methods. Five patients with a similar type C pelvic ring disruption who were all operated on using the same surgical technique and had RSA markers inserted at the time of surgery. All five patients had a unilateral comminuted sacral fracture lateral to the sacral foramina treated with posterior plating and pubic rami fractures stabilised by external fixation for six weeks. All patients were mobilised partial weight bearing after regaining leg control. RSA examinations at 2, 4, 12, 26 and 52 weeks included three radiographic pairs taken in supine, standing and supine positions at each time point. Two additional RSA examinations were performed the day prior and post pin removal at 6 weeks. Results. All patients ambulated before the 2 week follow-up and progressed uneventfully. At latest follow-up, there were no complications. Minimal displacements (translations less than 0.3mm and rotations less than 0.5°) were recorded between the supine exams pre and post standing at 2 weeks. Hence, the supine examination was found to be a reliable position to measure the migration of the ilium over time. No loss of reduction was identifiable on plain radiographs over time. At 52 weeks, in contrast to plain radiographic results, RSA measurements revealed that one patient had a fracture migration greater than 4mm. Such large displacements could result in sacral nerve root transection, leading to devastating consequences, such as incontinence, for patients whose sacral fractures are through or medial to the sacral foramina. In one patient, the migration recorded for the apparent uninjured posterior complex side exceeded the migration of the injured side suggesting an unrecognised bilateral injury. Comparative RSA examinations pre and post external fixator removal demonstrated that in three patients the injured hemipelvis migrated greater than 2mm after the removal of the external fixator, which may be indicative that the fixator was removed prematurely. Discussion and Conclusion. The application of RSA allows accurate measurement of pelvic fracture stability which is difficult, if not impossible, to identify and quantify with any other imaging techniques. Hence, RSA has the capacity to enable a better understanding of pelvic ring injuries and optimise their treatment