Research interests
Advanced study and research
Research interests focus on the epidemiology of osteoarthritis and osteoporosis. Based in the Botnar Research Centre with additional sessions at the MRC Lifecourse Epidemiology Unit at the University of Southampton. The programme has several major strands: (a) the intrauterine and genetic origins of osteoarthritis, osteoporosis and vitamin D metabolism; (b) the descriptive epidemiology of osteoarthritis and lower limb arthroplasty and (c) clinical trials in the management of common musculoskeletal conditions.
Expanding research programmes are based around: (a) the complex genetic and environmental influences on osteoarthritis and more importantly their interaction (in collaboration with UCSF and the University of Oxford): (b) the epidemiology of knee and hip osteoarthritis; (c) the epidemiology and survival of total joint replacements in osteoarthritis: (d) the role of bone in the pathogenesis of osteoarthritis; (e) translational research in the form of a number of clinical trials in osteoarthritis.
Further plans to clarify the risk factors for the incidence and progression of osteoarthritis, both radiographic and symptomatic, using a collection of large cohort studies. This work is funded by a large NIHR Biomedical Research Centre grant.
A rapidly developing area of research is the epidemiology of joint arthroplasty. An NIHR Programme grant has been awarded aiming to accurately define the predictors of a successful arthroplasty and its cost effectiveness. It will also produce an accurate and comprehensive risk prediction model for the success of joint arthroplasty.
The programme exploring the association between bone and osteoarthritis has two specific components: a) the effects of general bone size and density and, b) the effects of sub-chondral bone. We have shown that the association between systemic bone density and osteoarthritis is mainly driven by bone size and new data suggest the importance of bone shape. Further work in our existing cohorts using computerised tomography and conventional radiographs will further explore this important area of research. We will explore the role of sub-chondral bone using MRI and DXA in the VIDEO study, a large randomised trial of vitamin D in patients with OA. Its effect on the success of joint arthroplasty will be explored in the Oxford arthroplasty cohorts.
A number of randomised controlled trials in patients with osteoarthritis have been completed. The current largest study is a three-year trial of the vitamin D supplementation in patients with knee osteoarthritis. As well as determining the role of vitamin D, this study will provide insight into the important mechanisms involved in determining disease progression including: the calcium / vitamin D axis; muscle function; bone mineral density and genetic factors.
Osteoporosis
Published studies have demonstrated for the first time that the calcium/vitamin D axis can be permanently modified by subtle changes in the early environment. Furthermore, these changes are probably involved in mediating the effects of the early environment on the risk of developing osteoporosis. Studies in our cohort of children have demonstrated that maternal vitamin D concentrations and neonatal calcium concentrations at birth have significant effects on a child’s peak bone mass achieved during childhood, a finding which stimulated a large multi-centre grant application for a trial of vitamin D supplementation during pregnancy, which is successfully proceeding through the funding process. In our adult cohort we have demonstrated, for the first time, a significant interaction between birthweight and genetic factors (vitamin D receptor gene).
Current studies are characterising the interaction between the genome and early environment in the origins of osteoporosis, an important and essential step in combining the important progress achieved in each if these exciting fields. This is being performed in several cohorts: a) 2 cohorts of children exploring the effects on the acquisition of peak bone mass; b) cohort of elderly men and women exploring the effects on bone loss and fracture and (c) a randomised controlled trial of vitamin D supplementation in pregnancy. This will allow us to explore the role of several environmental factors, but focussing on vitamin D, in mediating the effect of the early environment on BMD.
A strong research interest in maintained in secondary osteoporosis. A large cohort of patients with inflammatory bowel disease to assess the rates and mechanisms of bone loss is being followed. We will uniquely use computed tomography in this group of patients to characterise accurately cortical versus trabecular bone loss. A similar cohort is being set up in adult patients with cystic fibrosis.
Other research
Collaboration with a number of local, national and international units to perform epidemiology studies within the fields of: rheumatoid arthritis, vasculitis, obesity and vitamin D metabolism.
Department(s)
Human Development and Health
Affiliate Department(s)
Human Development and Physiology
Research project(s)
To date the team at Southampton have led the development and validation of imaging techniques to uniquely determine the longitudinal epidemiology of forefoot complications in patients with rheumatoid arthritis (RA). This provides a substantial basis of expertise to develop work in this area, utilising improved technologies to address the unmet clinical burden of RA disease. A targeted intervention for forefoot complication in patients with RA will be necessary however there is currently limited evidence on which to tailor intervention to individual patients. As such the proposed research will use new generation US technology to facilitate patient assessment, within a community setting, in real time, the results of which will be used to inform a personalised medical approach to management.
Utilising an established Clinical Outcomes in Arthroplasty Study (COASt) cohort that is currently led by Professor Nigel Arden at both Southampton and Oxford sites; our aim is to determine whether clinical foot and ankle measures are useful in predicting patient reported outcomes following Total Knee Replacement (TKR).
It has been recognized that osteoarthritis (OA) of the foot may have a detrimental effect on patients’ health related quality of life and that foot OA may cause significant morbidity.The specific aims of this research were to develop a detailed understanding of the epidemiology, risk factors and associations of OA occurring within the feet in the general population at middle and older age. An additional aim was to determine lower limb biomechanical factors associated with radiographic foot OA.
Professor Nigel ArdenFaculty of Medicine, Room AB215, Mailpoint 801, South Academic Block, University Hospital Southampton, Tremona Road, Southampton, SO16 6YD
Room Number: SGH/MRC/MP95
Telephone:(023) 8077 7624
Facsimile:(023) 8070 4021
Email:N.K.Arden@soton.ac.uk
