Introduction. Approximately 20-25% of patients having joint replacement in the UK have moderate-severe frailty. Frailty is associated with poorer outcomes after joint replacement. Targeting frailty pre-operatively with exercise and protein supplementation could improve post-operative outcomes. Prior to conducting a randomised controlled trial (RCT), a feasibility study was necessary to inform trial design and delivery. Method. We conducted a randomised feasibility study with embedded qualitative work. Patients aged ≥65 years, frail and undergoing THR or TKR were recruited from three UK hospitals. Participants were randomly allocated on a 1:1 ratio to the intervention or usual care group. The intervention group had a 1:1 appointment with a physiotherapist and were provided with a home-based, tailored daily exercise programme and a daily protein supplement for 12 weeks before their operation, supported by six telephone calls from a physiotherapist. Questionnaires were administered at baseline and 12 weeks after randomisation. Interviews were conducted with 19 patients. Feasibility outcomes were eligibility and recruitment rates, intervention adherence, and acceptability of the trial and the intervention. Result. 411 patients were sent a screening pack. Of the 168 patients who returned a screening questionnaire, 79 were eligible and consented to participate, and 64 were randomised. Of the 33 participants randomised to the intervention, 26 attended the intervention appointment. Eighteen participants (69%) received all six intervention follow-up telephone calls. Nineteen participants completed an intervention adherence log; 13 (68%) adhered to the exercise programme and 11 (58%) adhered to the protein supplementation. The overall retention rate was 86% at 12 weeks. The 12-week follow-up questionnaire was returned by 84% of participants who were sent a questionnaire. Interviews found that the trial and intervention were generally acceptable, but areas of potential improvements were identified. Conclusion. This study demonstrated that a larger study is possible and has identified improvements to optimise the design of a RCT

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. Most western countries have implemented fast-track hip fracture aiming at surgery within 24 hours, since the mortality rate hereafter rises markedly. In Greenland, it is not achievable to operate within 24 hours. Arctic people live in sparsely populated areas and Greenland's population is scattered along the vast coastline. All patients must be chartered to Nuuk by airplane which can take up till several days to weeks, due to logistics and the Arctic weather. This presents a challenge regarding adhering to western guidelines. The operative delay may be acceptable though, as it is the impression that the Greenlandic population survives and endures better than patients of western populations. However, as data are lacking, we aimed to describe mortality among hip fracture patients in Greenland taking frailty and comorbidities into account. Method. All patients with ICD-10 codes DS720, DS721 and DS722 from 2018-2022 were identified as 261 patients diagnosed with hip fractures. Variables including time of diagnosis, time to operation, reasons for delay, ASA-score, Charlson Comorbidity index, time of death, and other possible confounding variables were analyzed. Primary outcome was mortality rates at 30-day post-OP and 1-year post-OP. Results. The average time from fracture to operation was 91.4 hours. In the Danish Cohort (DC) 70,6 % of patient were operated within 24 hours. Overall, 30-day mortality was 9,9 %, and 1-year mortality was 29,4 %, compared to the DC with 10,8 % 30-day mortality and 28,3 % 1-year mortality. Multivariate regression was conducted, showing no statiscal significant increase in mortality, despite extended delay. Conclusion. With no increase in death, the authors find it justifiable that patients in Greenland endure longer delays than the western population. The influence on further adverse effects needs to be investigated as well as causes of survival, but perhaps the Arctic people unveil mechanisms for raised survival among other populations

Introduction and Objective. Global prevalence of obesity has risen almost three-fold between 1975 and 2016. Alongside the more well-known health implications of obesity such as cardiovascular disease, cancer and type II diabetes, is the effect of male obesity on testosterone depletion and hypogonadism. Hypogonadism is a well-known contributor to the acceleration of bone loss during aging, and obesity is the single biggest risk factor for testosterone deficiency in men. Understanding the micro and macro structural changes to bone in response to testosterone depletion in combination with a high fat ‘Western’ diet, will advance our understanding of the relationship between obesity and bone metabolism. This study investigated the impact of surgically induced testosterone depletion and subsequent testosterone treatment upon bone remodelling in mice fed a high fat diet. Materials and Methods. Male ApoE. −/−. mice were split into 3 groups at 7 weeks of age and fed a high fat diet: Sham surgery with placebo treatment, orchiectomy surgery with placebo treatment, and orchiectomy surgery with testosterone treatment. Surgeries were performed at 8 weeks of age, followed by fortnightly testosterone treatment via injection. Mice were sacrificed at 25 weeks of age. Tibiae were collected and scanned ex-vivo at 4.3μm on a SkyScan 1272 Micro-CT scanner (Bruker). Left tibiae were used for assessment of trabecular and cortical Volumes of Interest (VOIs) 0.2mm and 1.0mm respectively from the growth-plate bridge break. Tibiae were subsequently paraffin embedded and sectioned at 4μm prior to immunohistochemical evaluation of alkaline phosphatase. Results. Trabecular bone volume and mineral density were significantly reduced in orchiectomised mice compared to sham-operated controls; and these parameters were normalised to control levels in orchiectomised mice treated with testosterone. In contrast, Trabecular thickness was significantly higher in testosterone depleted animals. Cortical bone parameters and body weights did not significantly differ between groups. Levels of alkaline phosphatase did not differ significantly in cortical or trabecular osteoblasts between groups. Conclusions. Findings suggest that testosterone deficiency significantly reduces trabecular bone parameters, and testosterone therapy may be a useful intervention for the loss of bone mass in testosterone deficient males. These results indicate that testosterone therapy may be useful for the treatment of trabecular bone frailty in testosterone deficient males. Observed changes in trabecular bone do not appear to be due to decreased mineralisation caused by osteoblast alkaline phosphatase. Ongoing work includes histology analysis to elucidate the mechanisms underpinning the changes seen in the bones of testosterone deficient animals

Sarcopenia is a progressive and generalized skeletal muscle disorder that involves loss of muscle mass and function. It is associated with increased adverse outcomes including falls, functional decline, frailty and mortality and affects 65% of people over the age of 65 more than half of people aged 80 and above. The factors that cause and worsen sarcopenia are categorised into two groups. The primary aetiological factor is ageing and the secondary factors include disease, physical inactivity, and poor nutrition. Sarcopenia is considered to be ‘primary' (or age-related) when no other specific cause is evident. However, a number of ‘secondary' factors may be present in addition to ageing. Sarcopenia can occur secondary to a systemic or inflammatory disease, including malignancy and organ failure. Physical inactivity is one of the major contributors to the development of sarcopenia, whether due to a sedentary lifestyle or to disease related immobility or disability. Furthermore, sarcopenia can develop as a result of inadequate protein consumption. Biomarkers are objective and quantifiable characteristics of physiological and pathophysiological processes. Biomarkers can be used to predict the development of sarcopenia in older susceptible adults and enable early interventions that can reduce the risk of physical disability, the co-morbidities associated with the loss of muscle mass and the poor health outcomes that result from sarcopenia. Non-invasive imaging technologies can be used as biomarkers to detect loss of skeletal muscle mass in sarcopenia include bone densitometry, computed tomography, ultrasound and magnetic resonance imaging. However, imaging requires sophisticated and expensive equipment that is not available in a resource poor setting. Therefore, markers of skeletal muscle strength and fitness and soluble biochemical markers in blood may be used as alternative biomarkers. Studies on sarcopenia have identified numerous soluble biochemical biomarkers. These biomarkers can be divided into two groups: “muscle-specific” and “non-muscle-specific” biomarkers. Since sarcopenia is associated with rapid skeletal muscle wasting, the skeletal muscle-specific isoform of troponin T may be considerate a useful biomarker of sarcopenia, since high troponin levels in blood are an expression of muscle wasting. Peptides derived from collagen type VI turnover may be potential biomarkers of sarcopenia. We have recently conducted a systematic review to summarize the data from recent mass-spectrometry based proteomic studies of the secretome of skeletal muscle cells in response to disease, exercise or metabolic stress in order to identify the proteins involved in muscle breakdown. Developing robust in vitro models for the study of sarcopenia using primary muscle cells is a high priority as is exploiting the in vitro models to understand catabolic and inflammatory processes and molecular mechanisms involved in sarcopenia. Co-cultures with adipose-derived and other cells may be used to screen for small molecules and biologicals capable of inhibiting the catabolic and inflammatory pathways involved in sarcopenia. This presentation reviews recent progress in this area and outlines opportunities for future research on sarcopenia

Introduction. Advanced stage and a large area of necrotic bone are known risk factors for failure after transtrochanteric rotational osteotomy of the hip in patients with osteonecrosis. The purpose of this study was to determine whether there were other risk factors for failure of this osteotomy. Methods. One hundred and five patients (113 hips) underwent transtrochanteric anterior rotational osteotomy for femoral head osteonecrosis and were followed for a mean period of 51 months post-operatively. Radiographic failure was defined as secondary collapse or osteoarthritic change. Multivariate analysis with the use of a Cox proportional-hazards frailty model was performed to assess factors that influenced the secondary collapse and osteophyte formation. A Kaplan-Meier product-limit method was performed to estimate survival. Results. Secondary collapse occurred in twenty-seven hips (23.9%) and fourteen of these hips (12.4%) were converted to a total hip arthroplasty. At the most recent follow-up, Merle d'Aubigne and Postel hip scores ranged from 6 to 18 points (mean, 16 points). Multivariate analysis showed that the stage of necrosis (hazard ratio=3.28; 95% confidence interval=1.49-7.24), age of the patient (hazard ratio=1.08; 95% confidence interval=1.02-1.14), body mass index (hazard ratio=1.19; 95% confidence interval=1.03-1.38), and extent of necrosis (hazard ratio=1.08; 95% confidence interval=1.04-1.11) were associated with secondary collapse. Seven of eighty-six hips without collapse progressed to osteoarthritis. Survivorship with total hip arthroplasty and radiographic failure as endpoints was 63.4% (95% confidence interval=51.1%-75.7%) and survivorship with total hip arthroplasty, radiographic failure, and loss of follow-up as endpoints was 56.0% (95% confidence interval=44.6%-67.4%) at 110 months. Conclusion. Our study showed that age, body mass index, stage, and extent of osteonecrosis were determining factors for secondary collapse, subsequent unsatisfactory clinical results, and conversion to total hip arthroplasty. These factors should be considered in patient selection for the osteotomy