Oxford Musculoskeletal Biomedical Research Unit
Created in April 2008 and funded by the National Institute for Health and Research, the NIHR Biomedical Research Unit in Musculoskeletal Disease at Oxford University Hospitals NHS Trust and the University (BRU) is a partnership of clinicians and researchers at the Nuffield Orthopaedic Centre NHS Trust and Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences and is one of three such units in the UK looking at this important clinical area. The unit supports a number of groups focusing on translational musculoskeletal research into prevention of disease, tissue engineering, joint replacement surgery and surgical technology and skill. Within the unit, a research-dedicated imaging suite is being developed, offering tools such as biplanar radiography and ultrasound scanning. It also includes the Oxford Musculoskeletal Biobank.
The work of the unit is also supported by patient and public involvement and many of the researchers are sharing recent insights via the Joint Ventures lecture series.
BRUs are at the forefront of a multi-million pound drive to prevent, diagnose and treat ill-health. The wider network also has centres looking at heart disease, nutrition, hearing problems and other conditions. See the NIHR website for information on Biomedical Research Units across the UK.
Professor Andrew Carr, Director of Oxford's Biomedical Research Unit, said research would focus on improving surgical skills, joint replacements and ground-breaking work on re-growing cartilage and tendon, which could ultimately transform the lives of thousands of patients around the world:
"Extraordinary numbers of people get pain because of musculoskeletal diseases such as osteoarthritis which accounts for over half of the reasons for people not being able to go to work."
Annual Reports
Achievements
- The initial period was judged to be successful and funding has been renewed until 2017
- We have published 59 papers acknowledging support from the NIHR
- We have recruited 2415 patients during 09/10 to 38 BRU projects
- We had 33 active grants in 2009/10, with an annual value of £1,809,903 associated with the BRU.
- We have commissioned the construction of a clinical trials unit as part of the BRU.
- We have improved support for post-graduate students.
- We are funding or part funding 9 post-graduate research students. 16 students are supervised by a BRU funded researcher.
- We have raised through charitable donation £5.5 million to build a 2000m sq extension of the Musculoskeletal Research Institute (the Botnar Research Centre) which will house part of the BRU and will focus on translational research (completion is anticipated by the end of 2013).
- We have secured funding agreements for £16 million from Oxford University and £18 million from the Kennedy Institute of Rheumatology Trustees to build a new research institute and to transfer approximately 80 researchers to Oxford.
- We have successfully joined the UK Capability Cluster in inflammatory joint diseases
- We collaborate significantly with other BRUs and BRCs and with the CLRN. Thames Valley CLRN funding for musculoskeletal studies has increased by 260% over the 2 years since the BRU opened.
Research Areas
Work is being done in the following areas, under the guidance of leading researchers:
A multi-cohort collaboration to define risk factors (focussing on vitamin D) and biomarkers and to develop a risk assessment model for progressive knee and hip Osteoarthritis (OA)
This programme of research will allow us to identify subjects at a high risk of developing OA and its associated symptoms and complications through the production of clinical risk tool using biomarkers (blood tests, urine tests, x-rays and MRI scans) and clinical data.
This will be helpful for doctors managing patients with osteoarthritis of the hip and knee in order to identify patients most at risk of developing severe disease allowing effective targeting of treatments. Additionally, it will be very helpful for future clinical trials of new treatments for osteoarthritis, by allowing the identification of the high risk populations to be recruited and the best biomarkers for monitoring the outcome.
The programme will also inform the extent to which subchondral bone just below the cartilage in the joint contributes to the pain and disability attributable to the osteoarthritis. Finally, It will clarify the role of vitamin D in retarding progression of knee osteoarthritis and define the best therapeutic intervention for further trials and informing public health policies.
AHP & Rehabilitation Research & Development
The Physiotherapy Research Unit (PRU) was established at the Nuffield Orthopaedic Centre in 1989. The aim of the unit is to promote research and evidence based practise in physiotherapy at local, national and international levels. The main activities of the Unit are to undertake primary research and disseminate findings, to assist clinical staff in research or audit projects and to provide research training and teaching to physiotherapists at both undergraduate and postgraduate level.
There are four main research strands:
- To evaluate function and outcome after joint arthroplasty
- To assess efficacy of specific physiotherapy treatment programmes on outcome, aiming to improve function
- To gain increased understanding about patients with chronic pain and how physiotherapy-based interventions improve well being
- To improve our understanding of disease features that cause disability eg. spasticity
To undertake this research we work closely with other BRU work streams eg. Arthroplasty led by Professor David Murray, as well as external collaborations.
The work package aims to advance our understanding of the contribution rehabilitation plays in patient outcome, improving function and patient satisfaction with the treatments they receive. Our longer term aim is to expand the focus of the unit to see contributions from a wider number of AHP groups.
Muscle and Tendon Ageing
Pain from degenerate and ageing muscle and tendon is a common cause of morbidity in the general population. Shoulder pain in particular affects around one quarter of the population and is the third commonest musculoskeletal disorder presenting in Primary Care in the UK. Many patients have symptoms which improve with simple conservative strategies within six months but approximately 25% of sufferers still have significant symptoms two years after onset. A significant proportion of sport and work related injuries are due to muscle and tendon pathologies.
The majority of shoulder pain is due to soft tissue disorders including tendonitis, tendon tear, bursitis and capsulitis. Natural history studies are rare and management pathways are unclear. Surgical repairs have high failure rates (20-60%) and widespread use of glucocorticoid injection may be harmful to tissue.
Our research programme has the following aims:
- Understand muscle and tendon pain mechanisms. Are there new ways to treat and/or prevent muscle and tendon pain?
- Establish a UK muscle and tendon tissue Biobank using a Research Network developed conjunction with the NIHR Comprehensive Research Network and HTA clinical trials programmes.
- Develop new imaging biomarkers using ultrasound and MRI.
- Understand age related cellular and molecular mechanisms, including oxidative and mechanical stress induced apoptosis.
- Determine the efficacy of new non-surgical treatment strategies including Vitamin C and Glucocorticoid injections and the use of human stem cells.
- Develop new surgical strategies with novel surgical repair implants and "Biopatches" to reduce rates of surgical repair failure.
Vitamin D and osteoporosis / Subchondral bone and osteoarthritis
Osteoporosis associated fractures represent a huge clinical burden, with over 70,000 hip fractures a year in the UK. A third of patients die within one year of their fracture and many are admitted to residential or nursing homes after discharge. We are testing the role of vitamin D supplementation in both preventing hip fractures (by improving bone growth of the developing foetus through supplementation of the pregnant mothers) and in improving recovery after a fracture (through high dose supplementation of patients after hip fracture to rapidly replete their vitamin D levels in the frail group of patients).
Osteoarthritis is the commonest cause of arthritis worldwide and an important cause of disability. We are leading research to examine the structure and function of the thin layer of bone that supports the knee and hip joints and how differences in this part of the bone may contribute to clinical symptoms such as pain in patients with osteoarthritis.
The new knowledge and understanding from these studies will translate into improved clinical care of patients through improving identification of patients at higher risk of severe disease and novel treatment options.
Arthroplasty - Research and Development
Joint replacement is an effective and widely used treatment for severe arthritis. Unfortunately some joint replacements fail or have a poor outcome and most do not provide the high levels of function demanded by the increasing number of younger, more active arthritic patients. The proposed research is directed towards decreasing the risks and improving the functional outcome and longevity of joint replacements.
The research has four strands:
- To identify patterns of arthritis, to investigate the underlying mechanical problems which might lead to therapies preventing arthritis developing or slowing its progress, and to improve joint replacement.
- To improve function after joint replacement particularly for more active patients.
- To look at reducing the failure rate of joint replacements, which will reduce the number of additional operations required.
- The research will look at understanding the causes of pain that some joint replacement patients suffer and improving treatment of pain after joint replacement surgery.
To undertake this research we have access to large clinical databases with long-term follow-up, excellent imaging facilities enhanced by support from the BRU, and we have recognised expertise in the area of hip and knee replacement. We are establishing a new programme of work in the area of pain in collaboration with experts in the field.
Arthritis in the young adult knee: indentifying and understanding early lesions, developing disease modifying treatments and following outcome of intervention
Treating the early arthritis in the knee to avoid the end-stages of disease is a major challenge. This works aims to improve our understanding of the cause of early OA disease, the drivers of progression and the different patterns of disease seen, enabling us to identify disease modifying opportunities. Creating new models of OA disease in the laboratory will allow further study of disease modifying agents at the cellular and molecular level. In order to study the effect of these interventions better means of measuring outcome are required.
This work will create a new patient related outcome measure for younger patients with early OA disease, enabling the effect of treatments to be followed in a more accurate way. This will be augmented by the development of a surrogate biological measure of treatment outcome, using synovial fluid from the joint. The work package aims to advance the field of early OA treatment, reducing the presently increasing need for joint replacement seen within the population.
Surgical Technology and Surgical Skills
With many surgical interventions the surgeon is a major factor in patient outcome. It is increasingly apparent that accuracy of implantation of joint replacements and acquisition of skill in minimally invasive surgery are crucially important determinants of patient outcome, particularly in the avoidance of complications and adverse incidents.
Newer minimally invasive approaches are more technically demanding and likely to result in greater variation in patient outcome in the future unless other methods of training and assessment of competence is developed. There are two initial projects:
- We have appointed a computer scientist and are developing virtual representations of joint anatomy suitable for simulating surgery. The first prototype will be a virtual reality training platform for the Oxford half knee replacement allowing surgeons to train and learn in a skills lab rather than on patients.
- We are examining the learning curves and skill loss over time for surgeons performing advanced arthroscopic procedures (eg. meniscal repair in the knee). These procedures are likely to play an important role in future rates of osteoarthritis and a need to understand how best to learn and subsequently perform these operations is needed.
Both these initial projects are now progressing well.