The burden of osteoporosis (OP), and its accompanied low energy fractures, is ever increasing. Targeted therapies are under development to stem the tide of the disease, with microRNAs identified as biomarkers and potential targets. Assessing the functional capacity of bone marrow mesenchymal stromal cells (BMSC) from patients with low energy neck of femur fractures (NOF) will identify the expected outcomes to be achieved from new, targeted osteogenic therapies.

Two patient groups were assessed; low energy NOF and osteoarthritic. Bone marrow aspirates were taken at time of arthroplasty surgery. The adherent fraction was cultured and assessed by flow cytometry, microRNA expression and differentiation functionality.

Both patient groups demonstrated characteristic extracellular markers of BMSCs. 3 key markers were significantly reduced in their expression in the NOF group (CD 90, 13, 166 P=0.0286). Reduced differentiation capacity was observed in the NOF group when cultured in osteogenic and adipogenic culture medium. 105 microRNAs were seen to be significantly dysregulated, with microRNAs known to be crucial to osteogenesis and disease process such as osteoporosis abnormally expressed.

This data demonstrates the impaired functional capacity of BMSCs and their abnormal microRNA expression in patients who suffer a low energy NOF. Future targeted therapies for OP must address this to maximise their restorative effect on diseased bone. The important role microRNAs can play as biomarkers and target sites has been further reinforced.

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.

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. 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. Upregulation of specific microRNAs has been identified in-vivo in osteoporotic patients. It is hypothesized that modulation of specific mircoRNA 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 upregulation 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 miRNA targeting.

There is an increasing trend towards radial head replacement (RHR) or fixation for complex radial head fractures. These injuries are identified by grossly displaced fragments or elbow instability. The aim of this study was to examine the outcome of a surgical protocol that emphasised delayed radial-head excision (RHE) as the procedure of choice. When the humero-ulnar joint was congruent, intervention was delayed 10 to 14 days to allow time for ligamentous healing. RHR was performed if instability was demonstrated on-table.

A retrospective study was performed to identify the outcome of patients undergoing surgery for a radial head fracture between 2008 and 2014. There were 18 Mason Type III and 18 Mason Type IV injuries. There was an associated coronoid fracture in 17 patients. RHE was performed in 28 patients, of which the reoperation rate was 2 (7.1%). RHR was performed in 15 patients, of whom 4 (27%) had reintervention. RHR was most common in the Type III coronoid fractures. The cumulative reoperation rate was 9.3% at six months and 15.4% at two years. The median Oxford Elbow Score (OES) was 85.4 (IQR 73.4 to 99.5). Time from injury was the only predictor of the Oxford Elbow Score (p=0.04).

This surgical protocol resulted in a reduced need for RHR, a low reintervention rate, and satisfactory function. RHR should be reserved for cases where stability cannot be achieved on-table. Stability can be maximised by delaying RHE until early ligamentous healing occurs.

Background

Aseptic loosening remains the primary reason for failure of orthopaedic implants. Therefore a prime focus of Orthopaedic research is to improve osteointegration and outcomes of joint replacements. The topography of a material surface has been shown to alter cell adhesion, proliferation and growth. The use of nanotopography to promote cell adhesion and bone formation is hoped to improve osteointegration and outcomes of implants. We have previously shown that 15nm high features are bioactive. The arrangement of nanofeatures has been shown to be of importance and block-copolymer separation allows nanopillars to be anodised into the titania layer, providing a compromise of control of order and height of nanopillars. Osteoblast/osteoclast stem cell co-cultures are believed to give the most accurate representation of the in vivo environment, allowing assessment of bone remodelling related to biomaterials.

Proximal femoral fractures remain the most common reason for admission to hospital following orthopaedic injury, with an annual cost of £1.7 billion to the National Health Service and social care services. Fragility fractures of the hip in the elderly are a substantial cause of mortality and morbidity. Revision surgery for any cause carries a higher morbidity, mortality, healthcare- and social economic burden. Which patients suffer failed surgery and the reasons for failure have not been established. The aim of this study was to determine which patients are at risk of failed proximal femoral fracture surgery, the mechanism and cause fo failed surgery and modifiable patient factors associated with failure of hip fracture surgery.

From prospectively collected data of 795 consecutive proximal femoral fractures admitted between July 2007 and July 2008, all peri-operative and post-operative complications were identified.

55 (6.9%) patients were found to have developed a surgical complication requiring further intervention. Risk factors included younger age (p=0.01), smoking (p=0.01) and cannulated screw fixation (p<0.01). Cannulated screw fixation was associated with a 30.9% complication rate. Mechanical cause was the most common reason for cannulated screw failure. Hip hemiarthroplasty most commonly failed by infective causes. Inter-trochanteric and subtrochanteric fracture fixation had very low failure rates. Surgical complication was not found to be associated with an increased mortality but a post-operative medical complication (21.8%) was associated with higher rate of mortality at 4-years (78.5%) and shorter time to mortality. (Median time 0.16 years (95% CI 0.00–0.33).

Background

BOA Guidelines recommend clinical and radiological follow-up after primary total hip arthroplasty (THA) at 1 and 5 years, and every 5 years thereafter to detect asymptomatic failure and allow early intervention. As revision surgery in asymptomatic patients is rare the need for routine follow-up in well-functioning individuals has recently been questioned. To evaluate the role of routine follow-up out-patient appointments (OPA) in identifying failing implants the modes of presentation for patients undergoing revision THA were reviewed.

British Orthopaedic Association (BOA) Guidelines recommend clinical and radiological follow-up after Total Hip Arthroplasty (THA) at 1 year, 5 years and every 5 years thereafter to detect asymptomatic failure. To evaluate the importance of routine follow-up appointments (OPAs) in detecting failing implants the presentation of patients undergoing revision THA was reviewed.

176 patients who received 183 first-time revision THAs over a seven-year period (2003-2010) were identified from an arthroplasty database. A preliminary study sampled 46 THAs in 45 patients. Retrospective chart review recorded symptoms and mode of presentation. Follow-up OPA costs were calculated to estimate savings.

All patients had symptoms at the time of revision (pain 96%, decreased mobility 76%, limp 35%, stiffness 26%, night pain 24%). Route of presentation was 80% new referrals (GP 63%, in-patient 9%, A&E 4%, Rheumatology 4%) vs 20% routine orthopaedic follow-up. The minimum cost for a routine follow-up OPA was £35. Assuming discharge after the earliest review when the patient has returned to full normal activities the estimated saving for the 2009 cohort of 377 primary THAs performed in our hospital is £13195 at 1 year and £52780 over the lifespan of the implants (assuming average 15 year survival).

Following uncomplicated primary cemented THA in our hospital asymptomatic implant failure is unlikely. Symptomatic patients tend to present mainly to their GP and other specialities, rather than orthopaedic follow-up OPAs. Early discharge after return to full normal activities would be safe and lead to significant financial savings.