Common hip condition may not always cause osteoarthritis in some racial groups

Contact: Amy Molnar
amolnar@wiley.com
John Wiley & Sons, Inc.

Osteoarthritis is the most common joint disorder worldwide, yet the cause of osteoarthritis of the hip is still unknown. One condition that may play a role is femoro-acetabular impingement (FAI), in which the femoral head of the thighbone causes damage by rubbing abnormally on the hip socket (acetabulum). FAI caused by an abnormality in the hip socket can lead to osteoarthritis, but it is not known if FAI that is not caused by a defect can also lead to the condition. Recognizing that the Asian lifestyle requires a larger range of hip motion than the Western lifestyle, a new study examined FAI in Japanese patients with normal hips. The study will publish online in the Journal of Orthopaedic Research (http://www.interscience.wiley.com/journal/jor), the official journal of the Orthopaedic Research Society.

Led by Mitsuyoshi Yamamura of Kyowakai Hospital in Osaka, Japan, researchers conducted a study on five healthy female volunteers between the ages of 18 and 26. They defined impingement using an open-configuration MRI, which allows imaging of the hip joint throughout the entire range of motion, by imaging subjects in the W-sitting position (in which the legs are bent behind the person) in two variations with the legs flexed to different degrees. Images were then obtained for 5 sitting positions, including sitting straight, bowing while sitting straight, sitting cross-legged, W-sitting, and squatting. Most of these positions are used in eating, socializing and in religious or traditional ceremonies and squatting is the position usually used for defecation in Asia and the Middle East.

The results showed that impingement occurred in all subjects in the W-sitting position and was also seen in 2 subjects in the squatting position. The largest hip internal rotation angle was seen in the W-sitting position. “No subjects complained of hip pain while maintaining any of the positions, even though the MR imaging process took from 10 to 14 minutes,” the authors note.

Populations in the Middle East and Asia have a low incidence of osteoarthritis in those with normal hips even though they regularly adopt positions that induce FAI, which suggests that FAI might not cause degenerative change in the hips. The researchers speculate that this may be related to soft tissue laxity around the hip, citing reports that joint laxity or range of motion differ by race. In addition, they note that impingement did not appear to be associated with pathology both in the present study and another study involving the shoulder area. Another reason FAI may not cause hip damage is that the positions in the study were static, as opposed to repetitive trauma, which the study did not evaluate.

The authors acknowledge that since the study was so small, the findings cannot necessarily be generalized to all Asian populations. Also, it is not known whether the subject in the study will develop osteoarthritis in the future. However, they note it is remarkable that FAI was seen in all 5 subjects. “This suggests that, depending on race, femoro-acetabular impingement might not always be a cause of osteoarthritis of the hip,” they conclude. “Further work in this area, including healthy males and patients with abnormalities, will confirm this conclusion.”

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Article: “An Open-Configuration MRI Study of Femoro-Acetabular Impingement,” Mitsuyoshi Yamamura, Hidenobu Miki, Nobuo Nakamura, Masakazu Murai, Hideki Yoshikawa, Nobuhiko Sugano, Journal of Orthopaedic Research, July 2007; (DOI: 10.1002/jor.20448).

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Aggressive nature of hand osteoarthritis

Contact: Rory Berrie
eularpressoffice@uk.cohnwolfe.com
44-790-069-8946
European League Against Rheumatism

Barcelona, Spain, Thursday 14 June 2007: In just two years, patients with hand osteoarthritis (OA) experienced a significant increase in pain and functional limitations, according to new data presented today at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain. Statistically significant radiological progression was also detected in 20% of subjects.

OA is the most common form of arthritis. It generally affects older people, especially women and can occur in multiple areas of the hand and wrist, causing pain and stiffness and affecting everyday activities requiring fine motor control and hand grip e.g. writing. Over time, if left untreated, the bones that make up the joint can lose their normal shape, causing further pain and limited motion. However, knowledge about the progression of hand OA and effective therapies to prevent its progression has been lacking.

Led by Dr Stella Botha-Scheepers of Leiden University, The Netherlands, this study followed 172 patients (mean age 60.5 years, 78.5% women) with hand OA (defined by the American College of Rheumatology criteria) for two years, assessing: pain intensity upon lateral pressure in the DIP, IP, PIP and CMC 1 joints on a four-point scale; self-reported hand pain and functional limitations with subscales of the Australian/Canadian Osteoarthritis Hand Index (AUSCAN LK 3.0); and osteophytes and joint space narrowing in the right and left DIP joints, IP joints of the thumbs, PIP joints and CMC 1 joints through standardized radiographs.

Despite a relatively short follow-up period of two years, statistically significant increases in pain intensity on lateral pressure standard response mean (SRM) 0.67), AUSCAN pain scores (SRM 0.25) and AUSCAN function scores (SRM 0.23) occurred. Statistically significant radiological progression was also seen in 20% of patients, in terms of joint space narrowing (SRM 0.34) and osteophytes (SRM 0.35), with progression of osteophytes occurring more often in women and middle-aged patients, and especially in women in an early post-menopausal stage.

Dr Botha-Scheepers commented: “The findings of this study underline the critical need for early, effective intervention in hand OA to prevent irreversible progression, given the dramatic deterioration of clinical and radiological disease status seen in just two years.”

Hand OA tends to appear in a predictable pattern, most commonly affecting the small joints of the fingers and the joint at the base of the thumb. It can be diagnosed by medical examination and X-rays of the hand. Treatment options for arthritis of the hand and wrist include oral medication, injections, splinting and surgery.

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For further information on this study, or to request an interview with the study lead, please do not hesitate to contact the EULAR congress press office on:
Email: eularpressoffice@uk.cohnwolfe.com
Rory Berrie: Onsite tel: +44 (0) 7900 698 946
Camilla Dormer: Onsite tel: +44 (0) 7725 328 983

Abstract number: OPO029

About EULAR

The European League Against Rheumatism (EULAR) is the organization which represents the patient, health professional and scientific societies of rheumatology of all the European nations.

The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.

Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 – 5 % of the adult population and are predicted to rise as people live longer.

As new treatments emerge and cellular mechanisms are discovered, the 8th Annual European Congress of Rheumatology in Barcelona (EULAR 2007) brings together more than 10,000 experts – scientists, clinicians, healthcare workers, pharmaceutical companies and patients – to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.

To find out more information about the activities of EULAR, visit: http://www.eular.org

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University of Manchester researchers reveal clues to new genes behind rheumatoid arthritis

07 Jun 2007

Researchers at the University of Manchester have identified evidence of several new genes behind the chronic inflammatory disease rheumatoid arthritis (RA), which affects 387,000 people in the UK.

Professor Jane Worthington and her team at the University’s arthritis research campaign (arc) Epidemiology Unit made their findings as part of the largest ever study of the genetics behind common diseases. The £9M Wellcome Trust Case Control Consortium (WTCCC), which today publishes its results in the journals Nature and Nature Genetics, has given a major boost to the understanding of genetics of seven common diseases, including RA. As well as providing insights into what leads some people to develop the diseases and offering new avenues for treatments, the success of the approach heralds exciting advances in the study of the genetics of disease. It has identified a wealth of genes implicated in coronary heart disease, type 1 and type 2 diabetes, Crohn’s disease, bipolar disorder and hypertension, as well as RA. Some of these genes are novel whilst others were known about and have been confirmed by the current study. Professor Worthington and her team have implicated several genes in the development of RA for the first time. Previously two genes were known to explain 50% of genetically determined susceptibility. Now the team have replicated their results for one of the new genes and are working to validate others. RA is a chronic inflammatory disease that can affect nearly all joints in the body, particularly the hands and feet. Complications such as lung disease can occur. In addition, patients with RA are more likely to die from cardiovascular disease and some cancers. Some people respond well to treatment, but most suffer a lifetime of disability. The team will now carry out further work to validate the findings and understand how the variation within key genes influences the development of RA, the course of the disease and the response to treatment. Dr Anne Barton, a clinician on the team, said: “These are exciting results as RA is a complex, heterogeneous disease with some people suffering inflammation of the hands and feet which comes and goes whilst others develop a progressive form which can quite rapidly result in marked disability. We believe the genes we have found may determine who develops RA or how the severe the disease becomes. “We also hope that this study may help us to discover why 40-50% of people do not respond to therapy. This therapy is expensive – £8,000 per patient per year for the newest biologic agents that block the inflammatory mediator TNF – and this work could show whether someone would respond well or not in advance, rather than by costly trial and error.” Professor Worthington said: “The WTCCC has been a fantastic example of collaborative effort in the UK. It has taken us to the place we are now, more rapidly and efficiently than if we had tried to undertake this study on our own. “We had 2,000 DNA samples from patients with RA. By contacting other RA clinicians and researchers in the UK, we now have a further 5,000 samples to take this work forward. “We are also indebted to the arthritis research campaign (arc), which provided the funding to collect the samples used. This was a huge investment, collecting samples from RA patients over two decades, but it was the sample collection which made it a high quality study.” Professor Peter Donnelly, Chair of the WTCCC, based at the University of Oxford, said: “Many of the most common diseases are very complex, involving both ‘nature’ and ‘nurture’, genes interacting with our environment and lifestyles. By identifying the genes underlying these conditions, our study should enable scientists to understand better how disease occurs, which people are most at risk and, in time, to produce more effective, more personalised treatments.” The £9 million WTCCC has been one of the UK’s largest and most successful academic collaborations to date, involving 50 leading research groups and over 200 scientists in the field of human genetics from dozens of institutions. For these papers, part of a number of studies due to be published over the next year, the researchers analysed 17,000 DNA samples taken from people in the UK – two thousand patients for each disease and three thousand control samples – to identify common genetic variations for seven major diseases. Although the human genome is made up of more than three billion sub-units of DNA, called nucleotides (or bases), most of these show little in the way of differences between individuals. The International HapMap Consortium and related efforts demonstrated that a substantial part of the variation in DNA sequence between individuals is due to single-nucleotide polymorphisms (differences), also known as SNPs. There are approximately 8 million common SNPs in European populations. Fortunately, because SNPs that lie close together on chromosomes often tell quite similar stories, researchers in the WTCCC were able to explore this variation through analysing a subset of these SNPs (in fact approximately 500,000). “Human genetics has a chequered history of irreproducible results, but this landmark collaboration of scientists in Britain has shown conclusively that the new approach of analysing a large subset of genetic variants in large samples of patients and healthy individuals works,” says Professor Donnelly. “We are now able to effectively scan most of the common variation in the human genome to look for variants associated with diseases. This approach will undoubtedly herald major advances in how we understand and tackle disease in the future.” The findings have been welcomed by Dr Mark Walport, Director of the Wellcome Trust, the UK’s largest medical research charity. The Wellcome Trust not only funded the WTCCC, but also co-funded the Human Genome Project and HapMap. “Just a few years ago it would have been thought wildly optimistic that it would be possible in the near future to study a thousand genetic variants in each of a thousand people,” says Dr Mark Walport, Director of the Wellcome Trust, the UK’s largest medical research charity, which funded the study. “What has been achieved in this research is the analysis of half a million genetic variants in each of seventeen thousand individuals, with the discovery of more than ten genes that predispose to common diseases. “This research shows that it is possible to analyse human variation in health and disease on an enormous scale. It shows the importance of studies such as the UK Biobank, which is seeking half a million volunteers aged between 40 and 69, with the aim of understanding the links between health, the environment and genetic variation. New preventive strategies and new treatments depend on a detailed understanding of the genetic, behavioural and environmental factors that conspire to cause disease.”For more information or to arrange an interview with Professor Jane Worthington or Dr Anne Barton contact University of Manchester Media Relations Officer Mikaela Sitford on 0161 275 2111. For information on The Wellcome Trust Case Control Consortium (WTCCC) contact WT Media Officer Craig Brierley on 0207 611 7329. For information on the paper in Nature contact Assistant Press Officer at Nature Helen Jamison on 0207 843 4658 or h.jamison@nature.com. Notes for editors 1. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. http://www.wellcome.ac.uk The Wellcome Trust Case Control Consortium was supported by: the Medical Research Council, British Heart Foundation, Juvenile Diabetes Research Foundation, Diabetes UK, the Arthritis Research Campaign, the National Association for Colitis & Crohn’s Disease and MDF The Bipolar Organisation 2. The University of Manchester Arthritis Research Campaign (arc) Epidemiology Unit aims to advance understanding of the major rheumatic and musculoskeletal disorders. The unit celebrated its 50th anniversary in 2004, and is one of the world-leading research groups in this field. Around 100 individuals work on a wide variety of different programmes and projects, and the size and strength of the unit permits it to undertake the very large scale, long-term prospective studies which are necessary to truly identify the cause of disease. Recent advances in genetics, molecular biology, biostatistics and computing have had major implications for the types of questions that can be answered using epidemiological methods.
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Largest ever study of genetics of common diseases published today

Contact: Craig Brierley
c.brierley@wellcome.ac.uk
44-207-611-7329
Wellcome Trust

The Wellcome Trust Case Control Consortium, the largest ever study of the genetics behind common diseases such as diabetes, rheumatoid arthritis and coronary heart disease, today publishes its results in the journals Nature and Nature Genetics.

The £9 million study is one of the UK’s largest and most successful academic collaborations to date. It has examined DNA samples from 17,000 people across the UK, bringing together 50 leading research groups and 200 scientists in the field of human genetics from dozens of UK institutions. Over two years, they have analysed almost 10 billion pieces of genetic information.

“Many of the most common diseases are very complex, part ‘nature’ and ‘nurture’, with genes interacting with our environment and lifestyles,” says Professor Peter Donnelly, Chair of the Consortium, who is based at the University of Oxford. “By identifying the genes underlying these conditions, our study should enable scientists to understand better how disease occurs, which people are most at risk and, in time, to produce more effective, more personalised treatments.”

The study has substantially increased the number of genes known to play a role in the development of some of our most common diseases. Many of these genes that have been found are in areas of the genome not previously thought to have been related to the diseases.

“Just a few years ago it would have been thought wildly optimistic that it would be possible in the near future to study a thousand genetic variants in each of a thousand people,” says Dr Mark Walport, Director of the Wellcome Trust, the UK’s largest medical research charity, which funded the study. “What has been achieved in this research is the analysis of half a million genetic variants in each of seventeen thousand individuals, with the discovery of more than ten genes that predispose to common diseases.

“This research shows that it is possible to analyse human variation in health and disease on an enormous scale. It shows the importance of studies such as the UK Biobank, which is seeking half a million volunteers aged between 40 and 69, with the aim of understanding the links between health, the environment and genetic variation. New preventive strategies and new treatments depend on a detailed understanding of the genetic, behavioural and environmental factors that conspire to cause disease.”

Amongst the most significant new findings are four chromosome regions containing genes that can predispose to type 1 diabetes and three new genes for Crohn’s disease (a type of inflammatory bowel disease). For the first time, the researchers have found a gene linking these two autoimmune diseases, known as PTPN2.

The study has also confirmed the importance of a process known as autophagy in the development of Crohn’s disease. Autophagy, or “self eating”, is responsible for clearing unwanted material, such as bacteria, from within cells. The may be key to the interaction of gut bacteria in health and in inflammatory bowel disease and could have clinical significance in the future.

“The link between type 1 diabetes and Crohn’s disease is one of the most exciting findings to come out of the Consortium,” says Professor John Todd from the University of Cambridge, who led the study into type 1 diabetes. “It is a promising avenue for us to understand how the two diseases occur. The pathways that lead to Crohn’s disease are increasingly well understood and we hope that progress in treating Crohn’s disease may give us clues on how to treat type 1 diabetes in the future.”

Research from the Consortium has already played a major part in identifying the clearest genetic link yet to obesity and three new genes linked to type 2 diabetes, published in April in advance of the main study. It has found independently a major gene region on chromosome 9 identified by independent studies on coronary heart disease.

Researchers analysed DNA samples taken from people in the UK – 2,000 patients for each disease and 3,000 control samples – to identify common genetic variations for seven major diseases. These are bipolar disorder, Crohn’s disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes. For each disease, the researchers will study larger population samples to confirm their results.

Although the human genome is made up of more than three billion sub-units of DNA, called nucleotides (or bases), most of these show little in the way of differences between individuals. A substantial part of the variation in DNA sequence between individuals is due to single-nucleotide polymorphisms (differences), also known as SNPs. There are approximately 8 million common SNPs in European populations. Fortunately, because SNPs that lie close together on chromosomes often tell quite similar stories, researchers in the Consortium were able to explore this variation through analysing a subset of these SNPs (in fact approximately 500,000).

“Human genetics has a chequered history of irreproducible results, but this landmark collaboration of scientists in Britain has shown conclusively that the new approach of analysing a large subset of genetic variants in large samples of patients and healthy individuals works,” says Professor Donnelly. “We are now able to effectively scan most of the common variation in the human genome to look for variants associated with diseases. This approach will undoubtedly herald major advances in how we understand and tackle disease in the future.”

Further analysis as part of the Consortium will be looking at tuberculosis (TB), breast cancer, autoimmune thyroid disease, multiple sclerosis and ankylosing spondylitis. The results are expected later this year.

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The Wellcome Trust Case Control Consortium, the largest ever study of the genetics behind common diseases such as diabetes, rheumatoid arthritis and coronary heart disease publishes its results in the journals Nature and Nature Genetics.

The £9 million study is one of the UK’s largest and most successful academic collaborations to date. It has examined DNA samples from 17,000 people across the UK, bringing together 50 leading research groups and 200 scientists in the field of human genetics from dozens of UK institutions. Over two years, they have analysed almost 10 billion pieces of genetic information.

Researchers have uncovered genetic variations for seven major diseases: bipolar disorder, Crohn’s disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes.

Speakers:

Dr Mark Walport – Director, Wellcome Trust

Professor Peter Donnelly (University of Oxford) – Chair, Wellcome Trust Case Control Consortium

Professor John Todd (University of Cambridge) – Type 1 diabetes

Dr Miles Parkes (Addenbrooke’s Hospital and University of Cambridge) – Crohn’s disease

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Projected state-specific increases in self-reported doctor-diagnosed arthritis and arthritis-attributable activity limitations

1: MMWR Morb Mortal Wkly Rep. 2007 May 4;56(17):423-5.

United States, 2005-2030.Centers for Disease Control and Prevention (CDC).

Arthritis and other rheumatic conditions (e.g., gout, lupus, and fibromyalgia) affect approximately 46 million adults in the United States, resulting in substantial disability and costs of $128 billion annually. Because U.S. adults are living longer and the number of persons in older age groups is growing, the number of U.S. adults living with chronic conditions such as arthritis likely will increase. The number of U.S. adults with doctor-diagnosed arthritis has been projected to reach nearly 67 million adults by the year 2030, including 25 million adults who are expected to have arthritis-attributable activity limitations. This report supplements those estimates by projecting the number of adults aged >/=18 years in each state who will have doctor-diagnosed arthritis and arthritis-attributable activity limitations in 2030. The results indicate that, among 48 states, the median projected increase in doctor-diagnosed arthritis from 2005 to 2030 will be 16%; a total of 14 states are projected to have increases of 30% to 87%. Greater use of existing evidence-based interventions and development of new interventions aimed at decreasing pain, improving function, and delaying disability associated with arthritis are needed to reduce the impact of these projected increases, particularly in those states that will be most heavily affected.

PMID: 17476205 [PubMed – indexed for MEDLINE]

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