Rheumatology research at North Bristol has strong links with the University of Bristol and the department of Clinical Science at North Bristol (CSNB). The head of Academic Rheumatology is Prof Jon Tobias, who is involved in a wide range of musculoskeletal research. The clinical lead for rheumatology research in North Bristol NHS Trust is Dr Paul Creamer. We have an excellent track record of rheumatology trainees obtaining fellowships from the Wellcome Trust and the Arthritis Research Campaign, to allow them to take Out of Programme Experience to focus full-time on research for three years.
Musculoskeletal Research in CSNB
The Academic Rheumatology group's research consists of laboratory, translational and epidemiological studies into the pathogenesis, diagnosis and treatment of osteoporosis.
We are investigating the determinants of bone development based on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, in collaboration with Professor George Davey-Smith, MRC CAiTE Centre, Department of Social Medicine. For example, we have recently been awarded a project grant from the Wellcome Trust of £428,000, to study the relationship between everyday levels of physical activity and bone development in the ALSPAC cohort, in late adolescence. The project will establish whether the skeleton responds to vigorous activities such as running and jumping, but not to less intense exercise such as walking. Understanding these relationships are important, since current recommendations for exercise in children largely focus on activities such as walking, which while beneficial for many disorders may have little impact in reducing the risk of osteoporosis in later life. The project will utilise accelerometers produced specifically for this project, which are capable of simultaneously recording exposure to activities of many different intensities. Activity data will be analysed in relation to parameters of skeletal development as assessed using a combination of whole body and hip DXA scans, and measurements obtained at the tibia using a low dose CT scanner.
We are also using the ALSPAC cohort to examine relationships between joint hypermobility and chronic pain in childhood, in a study being coordinated by Rita Doerner, in collaboration with Dr Jacqui Clinch at the Bristol Children’s Hospital, and Dr Shea Palmer at UWE.
Identification of vertebral fractures
Dr Emma Clark, arc Clinician Scientist Fellow, leads the Cohort for Skeletal health in Bristol and Avon (COSHIBA) study, intended to evaluate a new way of detecting patients with vertebral fractures in primary care. COSHIBA is a population-based primary care cohort of 3204 women aged 65 to 80. Women were recruited from 15 General Practices within the Bristol PCT area between October 2007 and April 2009. It was originally set up to run an RCT of a screening programme to identify women with undiagnosed vertebra fractures, with the outcome being appropriate bisphosphonate or other drug prescribing and cost-effectiveness of the screening tool. Additional work on the COSHIBA cohort includes studies on compliance with bisphosphonates, the psychological effects of being told you are at high risk of a vertebral fracture, and descriptive studies around the quality of back pain in women with vertebral fractures.
Genetic studies of high bone mass
Dr Celia Gregson, Wellcome Trust Clinical Research Fellow, is coordinator of the UK-wide DINAG study (DXA-databases to Identify Novel Anabolic Genes). This now constitutes 20 collaborating centres across the UK. A total of 959 DXA scans with a T score of 4 or more have been identified, from which 376 index cases have been established, with a further 60 likely. Index cases have been seen in Bristol, Bath, Cardiff and Yeovil. Index cases from Guy’s Hospital, St George’s Hospital and Oxford will be seen in the next two months. To date one LRP5 gene mutation has been identified and full sequencing is in progress. Bone turnover marker quantification is evolving from osteocalcin and P1NP assays, to consider adiponectin; recently linked with insulin sensitivity and fat mass.
Other translational studies
We perform translational studies into the cause and prevention of osteoporosis secondary to other conditions such as Inflammatory Bowel Disease (in collaboration with Professor Chris Probert, Department of CSSB) and Multiple Sclerosis (in collaboration with Professor Neil Scolding, Department of CSNB).
In laboratory studies, we are analysing the mechanisms involved in selective estrogen receptor modulator (SERM) effects on bone cells, in collaboration with Professor Craig McCardle, Department of Clinical Science in South Bristol (CSSB). Mark Perry leads a research program where we are characterizing the skeletal phenotype of novel mutant mice generated as part of the MRC ENU mutagenesis project, in collaboration with Professor Raj Thakker, University of Oxford.
NHS-based research in North Bristol
Many opportunities exist for clinical research at NBT. We are in a particularly strong position with a large, well documented, patient population and a very supportive Research & Development Department. Current projects include participation in a national prospective cohort study of newly diagnosed patients with RA (ERAN) and participation in a national double-blind placebo controlled trial of atorvastatin in patients with RA aiming to reduce cardiac risk (TRACE – RA study). We’ve recently completed the BIAS study (Bisphosphonates in Ankylosing Spondylitis, double-blind placebo controlled comparison of alendronate versus placebo in AS). Other projects undertaken within the last 10 years have included evaluation of MRI to measure cartilage volume in knee OA, in collaboration with AstraZeneca; the CARDERA study (evaluation of combinations of traditional DMARDs) and a study looking at an oral TACE inhibitor as a functional TNF blocker in RA. We have also supported clinical research undertaken by colleagues at the University of Bristol and UWE.
Logistically the simplest way to become involved in NHS research is by participating in multi-centre studies, though there is clearly scope for individuals to develop their own research interest if time and support permits.