Half Of Adults At Risk For Painful Knee Arthritis

A landmark government study suggests nearly one in two people
(46%) will develop painful knee osteoarthritis over their lifetime, with the highest risk among those who
are obese. According to the Arthritis Foundation, the study underscores the immediate need for the public
to understand what they can do to reduce the tremendous pain, disability and cost associated with arthritis.


Arthritis is exploding in an aging population of U.S. baby boomers. Nearly one in five U.S.
adults (46 million people) has arthritis and an estimated 67 million people will be affected by 2030.
Osteoarthritis, the most common type of arthritis, currently affects more than 27 million people in the
U.S.



The study, published in the September issue of Arthritis Care & Research, was conducted using
data from the Thurston Arthritis Research Center, University of North Carolina-based Johnston County
Osteoarthritis Project. It is one of the largest longitudinal studies to monitor the onset and progression of
knee and hip osteoarthritis in this country. While there were no significant differences in risk by sex, race
and education, the study found that nearly two in three people (65%) who are obese will develop knee
osteoarthritis over their lifetime. The study also found that those with a prior knee injury had a lifetime
risk of 57%.



"This groundbreaking research reaffirms the importance and need for Americans to take action to
prevent the problems that knee osteoarthritis can cause and to reduce its occurrence," said Janet Collins
Ph.D., director of the Centers for Disease Control and Prevention's National Center for Chronic Disease
Prevention and Health Promotion. "CDC's Arthritis Program works in partnership with states and
national organizations to promote arthritis self-management education and physical activity that help
people with arthritis improve the quality of their lives."



Most Americans are unaware of the seriousness of arthritis and the impact it can have on their
lives. Arthritis is the nation's most common cause of disability and costs the U.S. economy more than
$128 billion annually. Knee osteoarthritis, the most frequent form of lower extremity arthritis,
contributes to 418,000 knee replacement procedures annually and in 2006 accounted for 496,000 hospital
discharges and $19 billion in hospital charges.



"While Americans are looking forward to longer life expectancies than ever before, the reality is
that they will also be facing many more years of pain and disability," said Dr. John H. Klippel, president
and CEO of the Arthritis Foundation. "Obesity in this country is at an all-time high, putting millions at
risk for disabling arthritis. Coupled with sedentary lifestyles and an aging baby boomer population, we
are facing a public health crisis if Americans and Congress don't take action.



To reduce the pain and disability of arthritis, the Arthritis Foundation recommends the following:
Learn techniques to manage your arthritis. Participate in the Arthritis Foundation Self-Help
Program, a self-management course that teaches people with arthritis how to manage the pain and
challenges that arthritis imposes. The course has been shown to lead to a 40% reduction in pain.















Control weight. For those already living with symptoms, losing 15 pounds can cut knee pain in
half. Maintaining a healthy weight also can lower a person's risk of osteoarthritis. In fact, one
study showed that women who lost as little as 11 pounds halved their risk of developing knee
osteoarthritis and its accompanying joint pain.


Get active. Many people think that physical activity can worsen arthritis. Nothing could be
further from the truth. Physical activity can help decrease symptoms of osteoarthritis. In
addition, physical activity is an important component of weight control and helps maintain
healthy bones, muscles and joints. For joint-safe exercise programs, try the Arthritis
Foundation's Life Improvement Series land or water exercise programs.

"People need to know there are things they can do now to help themselves. These actions will
limit the impact of arthritis for both individuals and society as a whole," said Dr. Patience H. White, chief
public health officer of the Arthritis Foundation. For information on how to get started, visit
arthritis/prevent-osteoarthritis.php.



The Arthritis Foundation, according to Klippel, is also urging Congress to invest more in proven,
evidence-based public health strategies developed by the CDC that reduce the impact of osteoarthritis and
also to increase resources at the National Institutes of Health to find a cure for this debilitating disease.







About the Arthritis Foundation



The Arthritis Foundation is the leading health organization addressing the needs of some 46
million Americans living with arthritis, the nation's most common cause of disability. Founded in 1948,
with headquarters in Atlanta, the Arthritis Foundation has multiple service points located throughout the
country.



The Arthritis Foundation is the largest private, not-for-profit contributor to arthritis research in
the world, funding more than $400 million in research grants since 1948. Celebrating its 60th anniversary this year, the foundation helps individuals take control of arthritis by providing public health education; pursuing public policy and legislation; and conducting evidence-based programs to improve the quality of life for those living with arthritis. Information is available at arthritis/.



Source: Carol Galbreath


Arthritis Foundation

TNF-Alpha Inhibitors Will Continue To Dominate First- And Second-Line Biologic Therapy For The Treatment Of Rheumatoid Arthritis Through 2011

Decision Resources, one of the world's leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that tumor necrosis factor (TNF)-alpha inhibitors will continue to dominate first- and second-line biologic therapy for the treatment of rheumatoid arthritis in the United States through 2011, but the more established branded drugs such as, Centocor Ortho Biotech's Remicade, Abbott's Humira and Amgen/Wyeth's Enbrel, in this class will face competition from newer entrants. The decline in use for these established drugs will stem from physicians increasing their use of UCB's Cimzia and Centocor Ortho Biotech's Simponi and prescribing only one TNF-alpha inhibitor before moving out of the drug class completely.


"Rheumatologists we surveyed prefer to prescribe Enbrel as a first-line biologic compared with either Humira or Remicade and they tell us that this pattern will continue through 2011," stated Cindy Fung, Ph.D., analyst at Decision Resources. "In terms of total prescriptions, approximately one-half of the rheumatologists we surveyed anticipate a decline in their use of Remicade and one-third project a decline in their total use of Enbrel and Humira, stemming in part from physicians projecting an increase in the use of new agents in the TNF-alpha inhibitor class."The new Treatment Algorithms in Rheumatoid Arthritis report also finds that TNF-alpha inhibitors are not immune to competition from Roche's emerging IL-6 inhibitor Actemra upon its launch in 2010. Enbrel and Humira appear to be well insulated from this competition because they are well entrenched in the first two lines of therapy, but Remicade, Cimizia and/or Simponi are all at risk of losing patient share to Actemra.


The new Treatment Algorithms in Rheumatoid Arthritis report also finds that TNF-alpha inhibitors are not immune to competition from Roche's emerging IL-6 inhibitor Actemra upon its launch in 2010. Enbrel and Humira appear to be well insulated from this competition because they are well entrenched in the first two lines of therapy, but Remicade, Cimizia and/or Simponi are all at risk of losing patient share to Actemra.















By combining patient-level claims data with physician survey data, this report can be used to build patient-flow models and analyze the assumptions driving these models. Patient-level claims data show that 12.4 percent of Humira users went to it after using Enbrel, and only 1.9 percent of Humira users went to it after using Remicade. Survey findings suggest that physician perception about Enbrel's safety is a leading reason for its use ahead of Humira.


About Treatment Algorithm Insight Series


Decision Resources combines in-depth primary research with the most extensive claims-based longitudinal patient-level data from IMS Lifelink: Health Plans Claims database to provide exceptional insight into physicians' prescribing trends and the factors that drive therapy product choice, from diagnosis through multiple courses of treatment, for a specific disease.


About Decision Resources


Decision Resources is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources, Inc. company.


All company, brand or product names contained in this document may be trademarks or registered trademarks of their respective holders.


Source: Decision Resources



View drug information on Actemra; Cimzia; Enbrel.

MorphoSys Receives CTA Approval To Initiate Phase 1 Clinical Study For MOR103 Program

MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX) announced that the regulatory authorities in the Netherlands have approved the clinical trial application (CTA) to initiate a phase 1 study of the HuCAL-derived antibody MOR103. MorphoSys had submitted the clinical trial application in December 2007. In parallel, MorphoSys has received a manufacturing license from the Bavarian Government, allowing MorphoSys to release clinical trial material for MOR103 clinical studies as a sponsor.


MOR103 is a fully human HuCAL antibody directed against GM-CSF (granulocyte macrophage-colony stimulating factor), being developed in the area of inflammatory diseases, such as rheumatoid arthritis, where current treatment options are inadequate. Due to its diverse functions in the immune system, GM-CSF can be considered a target for a broad spectrum of anti-inflammatory therapies. The phase 1 trial is a randomized, double-blind, placebo-controlled, single-ascending dose trial and will be conducted in healthy volunteers. The study will evaluate the safety and tolerability as well as pharmacokinetics of escalating doses of MOR103.


"We are very pleased to see our first proprietary drug candidate advance quickly into the clinic," commented Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys AG. "The smooth process and quick approval by the Dutch authorities illustrate the quality of our clinical trial application process and the strength of the underlying data package."


About MorphoSys


MorphoSys is a publicly traded biotechnology company focused on the generation of fully human antibodies as a means to discover and develop innovative antibody-based drugs against life-threatening diseases. MorphoSys's goal is to establish HuCAL as the technology of choice for antibody generation in research, diagnostics and therapeutic applications. The Company currently has therapeutic and research alliances with the majority of the world largest pharmaceutical companies including Bayer-Schering, Boehringer Ingelheim, Centocor/Johnson & Johnson, Novartis, Pfizer and Roche. Within these partnerships, more than 40 therapeutic antibody programs are ongoing in which MorphoSys participates through exclusive license and milestones payments as well as royalties on any end products.


Additionally, MorphoSys is active in the antibody research market through its AbD Serotec business unit. The business unit has operations in Germany (Munich), the U.S. (Raleigh, NC) and U.K. (Oxford). For further information please visit morphosys/


HuCAL(R) and HuCAL GOLD(R) are registered trademarks of MorphoSys AG


This communication contains certain forward-looking statements concerning the MorphoSys group of companies. The forward-looking statements contained herein represent the judgment of MorphoSys as of the date of this release and involve risks and uncertainties. Should actual conditions differ from the Company's assumptions, actual results and actions may differ from those anticipated. MorphoSys does not intend to update any of these forward-looking statements as far as the wording of the relevant press release is concerned.

MorphoSys

Arthritis Pain 'Abolished' And Joint Damage Reduced With Experimental Gene Therapy

Early-stage research has found that a new gene therapy can nearly eliminate arthritis pain, and significantly reduce long-term damage to the affected joints, according to a study published in the journal Arthritis and Rheumatism. While the study was done in mice, they are the first genetically engineered to develop osteoarthritis like humans, with the same genetic predisposition that makes some more likely to develop the disease, the authors said. If all goes well with a follow-up study currently underway, researchers will apply to the U.S. Food and Drug Administration for permission to begin human trials next year.



Nearly everyone aged 65 or older suffers from the pain, swelling and permanent joint damage of osteoarthritis. The most common form of arthritis, it develops over time following initial joint injuries or just as a result of aging. In the current study, researchers found that one injection of a newly designed gene therapy relieved 100 percent of osteoarthritic pain in the study model. In addition, researchers were surprised to find that the therapy also brought about a nearly 35 percent reduction in permanent structural to joints caused by round and after round of osteoarthritic inflammation.



To date, treatment of arthritis is dominated by drug treatments like non-steroidal, anti-inflammatory drugs, COX-2 inhibitors and acetominophen. Morphine and its derivatives are still in common use as well, but can depress breathing and lead to addiction. Taken together, current treatments deliver inconsistent results and new approaches are needed, researcher said. Gene therapy has been attempted in the past, but older, invasive techniques required that therapeutic genes be injected directly into nerve cells. Strong pain relief resulted, but in some cases the injections caused nerve damage.



"Our publication represents the first proof that gene therapy can work in a way that is clinically applicable," said Stephanos Kyrkanides, D.D.S., Ph.D., associate professor of Dentistry at the University of Rochester Medical Center. "This therapy can simply be injected anywhere in an injured joint, and the treatment will find the nerve endings," said Kyrkanides, whose work on genetics in dentistry led to broader applications. The common ground between arthritis and dentistry: a common site of arthritic pain is the jaw joint.



Study Details



Proteins called receptors are built into the outer surfaces of human cells, enabling them react to the nutrients, toxins and hormones around them. Each receptor is designed to react with a specific signaling molecule, which docks into the receptor like a ship coming into port. The docking changes the shape of the dock to set off chain reactions inside the cell, enabling it to respond to the signal. On nerve cells for instance, certain receptors are shaped to accept naturally occurring painkillers called opioids, which when they dock, prevent the sending of pain messages along nerve pathways.
















In the current study, researchers used gene therapy to increase by about one thousand times the number of opioid receptors expressed on the surfaces of nerve cells that carry pain messages back and forth between an osteoarthritic jaw joint and the spinal cord. Thus, nerve cells involved in pain transmission, with so many more receptors on their surfaces, became drastically more responsive to the naturally occurring painkiller, researchers found.



Gene therapy inserts tailor-made genes into cells that can, for instance, direct cells to build more of a needed protein. To deliver the genes into cells, researchers use harmless viruses called vectors, which have evolved to invade human cells and insert their DNA. In designing the new therapy, Kyrkanides' team chose to work first with vectors based on feline immunodeficiency virus (FIV), a lentivirus that attacks the immune system of cats. It resembles HIV in humans, but is incapable of causing human infection.



Despite the strong results, however, the team will seek to deliver the same gene therapy with a different vector in the next phase of experiments. Kyrkanides is partnering with researchers at the National Institute on Drug Abuse, part of the National Institutes of Health, to see whether the same therapeutic gene can be delivered instead by an adeno-associated vector (AAV). AAVs have already been approved as safe for experimental gene therapy by the U.S. Food and Drug Administration, eliminating a tremendous regulatory hurdle. If successful, this next study will provide the proof of principle needed for the team to apply for phase I human clinical trials, perhaps within 18 months, Kyrkanides said. Early results, while not yet published, suggest that one serotype of the AAV vector they are working with will provide results comparable to FIV.



Beyond the current study, Kyrkanides' work has contributed to the emerging theory that pain is not a symptom of osteoarthritis, but is instead part of the disease. According to this new paradigm, pain is composed of nerve messages that over time cause permanent chemical changes in the pathways they travel along, making them more sensitive to pain and encouraging inflammation. This two-way "crosstalk" may mean that arthritis in one joint can spread, through the central nervous system (CNS), to other joints. Worse yet, joint arthritis may export inflammation to the brain, where it plays a role in neurological conditions (e.g. Alzheimer's disease, dementia and multiple sclerosis).



While the just published study involved a technique that delivers gene therapy by injection at the joint, other promising approaches may involve interrupting crosstalk in the brain instead. Based on that promise, the Medical Center is in the process of founding a private biotech company to develop the technology. It would search for new drugs that interfere with key inflammatory receptors on sensory nerve cells within the CNS.



Joining Kyrkanides in the publication from the University of Rochester School of Medicine and Dentistry were co-authors J. Edward Puzas, Ph.D., Donald & Mary Clark Professor of Orthopaedics, M. Kerry O'Banion, M.D., Ph.D., associate professor of Neurobiology and Anatomy and Ross Tallents, D.D.S., professor of Dentistry and director of the Orofacial Pain Program within the University of Rochester's Eastman Dental Center. Student contributors were Paolo Fiorentino, Yanjun Gan, Yu-Ching Lai and Solomon Shaftel. Jennie Miller was involved as Kyrkanides' technical associate. Maria Piancino, of the University of Torino, Italy, was also an author based on an alliance between the two institutions. The study was funded in part by the National Institute of Dental and Craniofacial Research.



"Near future applications of the work may include amplifying the body's response to morphine, drastically reducing the amount needed for powerful pain relief," Tallents said. "A little further out, the new idea that peripheral inflammatory diseases like arthritis can lead to brain inflammation may provide an entirely new way to treat inflammatory neurological conditions that affect millions."






Contact: Greg Williams


University of Rochester Medical Center

Grape Powder Alleviates Joint Inflammation - Constituents In Grapes Have Antihyperalgesic Effects In A Rat Model Of Joint Inflammation

Johns Hopkins Researchers at Neuroscience 2008 - Table grapes are high in flavonoids, which are thought to have strong antioxidant and anti-inflammatory properties. Now, researchers at the Johns Hopkins University School of Medicine have shown that powdered grapes appear to reduce pain and inflammation in a rat model of arthritis, where rats knees are inflamed using a chemical injection.


Some rats were fed the powdered equivalent of 10 cups of grapes once a day after the arthritis-inducing injection, while others got only sugar water. Over the course of four days after the chemical injection, the researchers tested the rats' inflammation levels and pain responses by measuring their sensitivity to mechanical stimulation such as prodding their paws and measuring the amount of knee swelling. Rats fed grape powder could withstand stronger prodding than their sugar-fed counterparts.


The researchers also compared the grape powder treatment with a common nonsteroidal anti-inflammatory drug, meloxicam, and found that while the dose of meloxicam alone was not sufficient to reduce pain, animals fed a combination of grape powder and meloxicam experienced even less pain from their arthritis than animals that received either substance alone. The combination treatment also reduced the knee swelling associated with inflammation.


"I think there are two important messages here," says Jasenka Borzan, Ph.D., a research associate in anesthesiology at Hopkins. "That consuming flavonoids through natural products like grapes can be beneficial to health in general and also specifically for reducing inflammatory pain; and that consuming natural products like grapes may also be beneficial in reducing the amount of medication necessary to reduce inflammation."



Johns Hopkins Medicine

hopkinsmedicine

Study To Assess Hip Exercises As Treatment For Osteoarthritis In The Knee Joints

Researchers at Rush University Medical Center are testing a novel regimen of hip-muscle exercises to decrease the load on the knee joints in patients with osteoarthritis. The goal is not only to relieve pain but also, possibly, to halt progression of the disease.


"Each time you take a step, a load, or force, is placed on the knee joints. How much load depends not just on your weight, but also on the way you walk and the alignment of your leg," said Laura Thorp, PhD, assistant professor of anatomy and cell biology at Rush Medical College and principal investigator for the study. "If we can appropriately alter the gait patterns of patients with osteoarthritis, we can minimize the load and relieve pain.


"Ultimately, we're hoping we can prevent the disease from advancing. No treatment currently exists that can stop osteoarthritis from progressing in the knees, other than joint replacement surgery."


Osteoarthritis is the most common form of arthritis and a significant source of disability and impaired quality of life. A higher-than-normal load on the knees during walking is a hallmark of the disease, associated with both the severity of the osteoarthritis and its progression, according to Thorp.


Thorp is enrolling patients with mild to moderate osteoarthritis in their knees in a research study to determine the effectiveness of certain hip exercises in treating the disease. Study participants have their knees x-rayed and undergo an initial assessment in Rush's Human Motion Laboratory to measure the load on their knee joints while walking. Participants then follow a specific regimen of hip exercises for four weeks under the direction of Charles Cranny, clinical manager of outpatient physical therapy.


The exercises focus on strengthening the hip abductor muscles, such as the gluteus medius, a broad, thick, radiating muscle that helps to stabilize the pelvis during ambulation. In patients with osteoarthritis in the knees, these muscles tend to be weak, causing the pelvis to tilt toward the side of the swing leg when walking, instead of remaining level with the ground, which increases the load on the knee joints. Strengthening these muscles helps the pelvis and the knee remain in better alignment, and thereby lessens the load.


After the four weeks of supervised physical therapy, participants are reassessed to determine whether the load on the knees has decreased, and whether the pain has subsided.


The trial continues for another four weeks, with patients exercising at home to determine whether the adjustments in gait can be maintained.


According to Thorp, exercise regimens to date have focused largely on strengthening the quadriceps and hamstring muscles, which stabilize the knee joint but likely do little to correct alignment with the rest of the leg or alter the load on the joint.


Preliminary evidence in the present trial has already shown that a decrease in load is attained with hip-muscle exercises.


"By lessening the load on the knees, we can remove one of the major known risk factors for the progression of osteoarthritis," Thorp said.


Rush University Medical Center includes a 674-bed (staffed) hospital; the Johnston R. Bowman Health Center; and Rush University (Rush Medical College, College of Nursing, College of Health Sciences and the Graduate College).
Rush's Human Motion Laboratory has a complete three-dimensional motion measurement system consisting of a multi-camera optoelectronic device and a multi-component force plate for the measurement of foot-ground reaction force. The facility has been used in clinical trials sponsored by industry and the National Institutes of Health. The facility also provides information for planning surgical interventions and non-surgical treatments for patients with osteoarthritis.


Source: Rush University Medical Center

Data Does Not Indicate Glucosamine Damages The Liver

The COT (Committee on Toxicity) has published its findings on whether glucosamine might cause hepatitis. Glucosamine is a popular food supplement; it is commonly taken together with chondroitin for patients with osteoarthritis.


The COT looked into whether there might be a link between glucosamine intake and hepatitis risk after a small number of case reports.


The COT concludes that after looking at available data on glucosamine, no link could be found with damage to the liver. Glucosamine is present naturally within our bodies, and there is no plausible mechanism by which damage to the liver might be caused.


The COT looked at case reports, human trials data, laboratory animal studies, as well as data on chondroitin.


The Food Standards Agency, United Kingdom, believes that there is no current evidence to suggest that glucosamine raises the risk of developing hepatitis.


Source - Food Standards Agency, UK.
Related articles

NIH GAIT Study Supports Use Of Glucosamine And Chondroitin For Osteoarthritis Treatment
Multiple Sclerosis - OTC Glucosamine may provide some relief
Knee Arthritis Did Not Benefit From Supplements

Written by .

New insights into arthritis drug

Contact: Michael C. Purdy

purdymmsnotes.wustl

314-286-0122

Washington University School of Medicine(USA)


St. Louis (USA) -- Researchers at the Veterans Affairs (VA) Medical Center and Washington University School of Medicine in St. Louis have analyzed a national database of VA patients to investigate the effects of the rheumatoid arthritis drug leflunomide in the first years after its approval.


The Food and Drug Administration (FDA) approved the use of leflunomide for rheumatoid arthritis in October 1998 and recommends starting treatment with high doses to rapidly trigger the drug's benefits.

But the study, which appears in the Dec. 15 issue of the journal Arthritis Care & Research, shows that such high doses may cause adverse side effects that lead some patients to stop taking the drug.



The findings may prompt physicians to consider slightly modifying the standard leflunomide treatment regimen.



'Our data suggest that by starting on a lower dose initially, patients tolerate the drug better,' says Seth Eisen, M.D., a VA staff physician and professor of medicine and psychiatry at the School of Medicine. 'The disadvantage is that it may take a little bit longer for patients to improve clinically; the advantage is that patients may be more likely to continue treatment.'



Eisen and Chuck Siva, M.D., a rheumatology fellow, were principal investigators of the study, which was conducted in collaboration with several other VA medical centers across the country.



Rheumatoid arthritis, one of the most crippling forms of arthritis, afflicts about 2 million Americans with joint pain and inflammation. It is a chronic condition linked to immune system malfunctions. Leflunomide is one of about a dozen drugs available for treatment.



In addition to suggesting an alternative approach to initial treatment, the new findings also help put to rest lingering concerns about whether leflunomide's toxicity was adequately assessed in phase III FDA clinical trials that ended in 1998.



'As far as we could tell there were no surprises in terms of toxicity,' Eisen says. 'Sometimes it takes a lot more patients than the 3,300 we studied to pick up rare adverse outcomes, but I think our findings are reassuring to the larger community of patients and clinicians.'



Eisen emphasizes that since the study is a review of already existent data, no control and intervention groups could be established and assessment of side effects could not be standardized.



'In a subset of the patients for whom the medication was discontinued, we examined their medical records in an attempt to determine the reason the medication was stopped,' Eisen explains. 'We were particularly looking for evidence of severe toxicity and did not find any. But still, it's a matter of trying to interpret clinical notes.'
















Although researchers were aware of the disadvantages of this type of study, there also are a number of potential advantages. Only a relatively small investment of money and time were required, and the patient population at the VA offered a chance to study portions of the general population that typically do not enroll in clinical trials.



Eisen explains that clinical trials often enroll more women and younger patients from higher socio-economic groups. The sex bias is particularly prevalent in clinical trials for treatments for rheumatological diseases, which afflict women more often than men.



'VA medical data complements information obtained from other sources because VA patients are predominantly male and older and include a higher proportion of African-Americans and individuals from lower socio-economic groups than general studies do,' Eisen says.



The scientists' work with VA database records was closely monitored by the VA's Human Studies Committee to ensure patient information was appropriately accessed and used.



Eisen suggests that researchers should consider conducting studies like this on other drugs already approved for clinical use.



'Post-approval follow-up is very important because it may demonstrate problems, sometimes decades later, that weren't appreciated,' Eisen says, citing the example of premarin, a treatment for post-menopausal symptoms. Risks recently linked to the drug were only identified several decades after it was approved for clinical use.



'Because post-approval studies tend to require large numbers of people in order to evaluate the less-common adverse outcomes, they are typically very, very expensive to do,' Eisen says. 'Studying large databases like the VA's is relatively inexpensive, and it is very feasible to collect and analyze important information.'



C Siva, S Eisen, R Shepherd, F Cunningham, MA Fang, W Finch, D Salisbury, J Singh, R Stern, SA Zarabadi. Leflunomide use during the first 33 months after FDA approval: experience with a national cohort of 3,325 patients. Arthritis Care & Research, Dec. 15, 2003.



Funding from the Arthritis Foundation and Washington University School of Medicine supported this research.



The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


View drug information on Premarin.

Knee Arthritis Did Not Benefit From Supplements

US scientists found that the dietary supplements glucosamine and chondroitin sulfate were no more effective than placebo at slowing down the rate of
cartilage loss in the knees of patients with osteoarthritis; however they also said the trial was probably too short and too small, and spoke more
to scientists about how to conduct further research in this area than than to patients.


The two-year multicenter study was the work of rheumatologist Dr Allen D. Sawitzke, associate professor of internal medicine at the University of Utah
School of Medicine in Salt Lake City, and colleagues from other research centers throughout the US, and is published online in the October issue of
Arthritis & Rheumatism.


Osteoarthritis of the knee is a condition where the cartilage that cover the surfaces of hard bone on the inside of the knee joint, and the synovial fluid in
the joint, gradually reduce, resulting in loss of cushioning and lubrication and space between the femur and tibia causing inflammation and pain.


Treatment is limited to symptom relief, wrote the authors, and there are no therapies that slow down the loss of cartilage. Of the 21 million Americans with
osteoarthritis, many take the dietary supplements glucosamine and chondroitin sulfate, either alone or in combination, to relieve pain.


For this study, Sawitzke and colleagues evaluated the effect of glucosamine and chondroitin sulfate (alone and in combination), as well as celecoxib and
placebo on progressive loss of joint space width (as shown by X-ray) in patients with osteoarthritis of the knee.


The researchers enrolled 572 participants who were already taking part in a 2-year trial to evaluate the pain relieving properties of glucosamine and
chondroitin (this was the multicenter, randomized, national clinical trial known as GAIT, which stands for Glucosamine/Chondroitin Arthritis Intervention
Trial).


The participants were in 5 groups, each continuing to take either glucosamine at a dose of 500 mg 3 times a day, chondroitin sulfate at a dose of 400 mg 3
times a day, a combination of glucosamine and chondroitin sulfate, celecoxib at a dose of 200 mg a day, or placebo over 24 months. All the participants met
the criteria of at least 2 mm of joint space width and certain other radiographic criteria when they started. Patients who had mostly lost cartilage at the
sides of the joint (lateral compartment narrowing) were excluded.


The researchers measured the joint space width of each patient by X-ray at the start of the study (baseline) and then at months 12 and 24. The main measure
they used in their analysis was the mean change in joint space width from the start of the study.


The results showed that:

In the placebo group, the mean loss of joint space width at 2 years was 0.166 mm (after adjusting for design and clinical factors).

No statistically significant difference in mean loss of joint space width was found in any treatment group compared with the placebo group.

Less severely affected knees (Kellgren-Lawrence grade 2), but not more severely affected knees (Kellgren-Lawrence grade 3), in the treatment groups showed a trend toward
improvement relative to the placebo group.

The authors said that the power of the study was hampered by the small size of the sample, the variance of joint space width, and a smaller than expected
loss in joint space width. They concluded:















"At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW [joint space width] loss as compared with placebo.
However, knees with K/L grade 2 radiographic OA [osteoarthritis] appeared to have the greatest potential for modification by these treatments."


In a separate statement Sawitzke said:


"At two years, no treatment achieved what was predefined to be a clinically important reduction in joint space width loss."


"While we found a trend toward improvement among those with moderate osteoarthritis of the knee in those taking glucosamine, we were not able to draw any
definitive conclusions," he added.


The problem with interpreting these results, explained the statement, is that the joint space width loss of the placebo group was much
lower at two years than the 0.4 mm the researchers expected. From previous studies, they expected that a loss of 0.2 mm or less at two years meant a slowed rate of
cartilage loss, and because the reduction in rate of joint space loss for all the groups was under this threshold, they had to concluded there was no effect
on joint space loss by any of the agents.


Dr Josephine P Briggs, director of the National Center for Complementary and Alternative Medicine, one of the funders of the study, said "the results of the
study provide important insights for future research."


Co-investigator Dr Daniel O Clegg said the trial shed light on how osteoarthritis progresses, gave them insight into techniques that can measure joint space
width loss more reliably, and on how glucosamine and chondroitin sulfate may potentially affect joint space width. He said it also helped them to identify
patients who may respond better in future research.


"The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: A report from the glucosamine/chondroitin arthritis
intervention trial."

Allen D. Sawitzke, Helen Shi, Martha F. Finco, Dorothy D. Dunlop, Clifton O. Bingham III, Crystal L. Harris, Nora G. Singer, John D. Bradley, David Silver,
Christopher G. Jackson, Nancy E. Lane, Chester V. Oddis, Fred Wolfe, Jeffrey Lisse, Daniel E. Furst, Domenic J. Reda, Roland W. Moskowitz, H. James Williams,
Daniel O. Clegg.

Arthritis & Rheumatism, Volume 58 Issue 10, October 2008, pp 3183-3191, Published Online: Sep 29, 2008.

DOI: 10.1002/art.23973


Click here for Abstract.


Source: Journal abstract, University of Utah Health Sciences.


Written by: , PhD.

Knee pain often linked to pain elsewhere in the body

Joint pain, especially in the knees, is a common complaint in older patients and can impact quality of life. A team of researchers recently set out to examine how often knee pain is accompanied by pain elsewhere in the body and whether the presence of multiple joint pain affects older patients' general health and psychological status. Their findings, published in the August 2005 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis.), indicate that most people with knee pain also have pain at other sites and these patients tend to have more limited physical function and suffer more from depression and anxiety.


Led by Peter Croft of Keele University in Keele, UK, the authors surveyed a total of 5,364 patients aged 50 years or older who were registered with 3 general practices in North Staffordshire, UK. Each participant completed a questionnaire that included a body manikin on which they shaded any areas where they had experienced pain for one or more days during the last month. Pain was categorized into regions, which included: knee, neck, hand, lower back, hip, and foot and ankle. Based on where the pain occurred, participants were then grouped into (i) those with no pain at all, (ii) those with knee pain, either alone or with pain in 1 or 2 or more locations elsewhere, (iii) those with no knee pain but with pain in 1, 2 or 3 or more locations other than the knee.


A standard health survey used to determine the influence of pain elsewhere on general health was also completed, as well as an index to measure pain and disability specifically related to the knee. Obesity, anxiety and depression, all of which are linked to widespread pain, were also measured using various scales.


Of those surveyed, slightly more than one-third (1,909) ended up in the no pain group, 41% (2,210) in the knee pain group, and 23% (1,245) in the pain elsewhere group. Decreased physical function increased with the number of pains in the body, both in the knee and elsewhere. In those with at least 3 pain regions, the subgroup that included knee pain had worse physical function. This group was also more likely to be depressed than either those with no pain at all or those who had pain in a location other than the knee, even if it was in 3 or more regions.


The results indicate that knee pain does not tend to occur by itself, and that when it occurs with pain in other regions, it is associated with poorer general and psychological health. In addition, the results suggest a link between the extent of pain in the body and the impact of pain in a particular region. "We have shown that knee-specific pain and disability are actually worse in the presence of pains elsewhere than the knee, even after accounting for poorer psychological health," the authors state.


"The practical importance of our findings is that the presence and extent of pain in other sites may be an important determinant of outcome in patients who present with knee pain, just as it appears to be in those who present with back pain [as shown in previous studies]," the authors conclude. In addition, they note that managing pain in one region such as the knee (with local treatments such as physiotherapy or total knee replacement) might have beneficial effects on the general perception of pain and on the frequency and impact of pains elsewhere in the body.


Article: "'Pain Elsewhere' and the Impact of Knee Pain in Older People," Peter Croft, Kelvin Jordan, and Clare Jinks, Arthritis & Rheumatism, August 2005; 52:8; pp. 2350-2354. Article is available via Wiley InterScience at interscience.wiley/journal/arthritis.

Over Half Of People With Rheumatoid Arthritis Have Periodontitis

Over half (56%) of people with rheumatoid arthritis (RA) also have periodontitis (a chronic inflammatory disease of the gum and surrounding ligaments and bones that hold the teeth in place), displaying fewer teeth than healthy matched controls, high prevalence of oral sites presenting dental plaque and advanced attachment loss (the extent of periodontal support that has been destroyed around a tooth) (chi square p

Total Body Scans: The Glass Body In 40 Seconds / ECR 2007

Less than ten years ago it took several hours to complete a scan on a patient with computer or magnetic resonance tomography. That was an unreasonably long scan time and in the case of CT, also entailed extremely high exposure to radiation. Today, MRT scanners image with up to 72 coils at the same time; CT units scan 64 slices at a time and in lab tests as many as 256. The rotors that move the imaging units around the patient to produce the slice images now have much greater rates of acceleration. An increasing number of MRT units operate today with parallel imaging and have a field strength of 3 Tesla instead of the customary previous strength of 1.5 Tesla. This means more sharply focused images in less time. The problem of venous overlay, i.e. veins overlying the arteries in the image, has also practically been solved.


Precise images taken in an ultra-short time allow for whole body screenings to be performed if disease is suspected.


As a result, today it takes a treating physician just 40 seconds to render the inner workings of an entire human body visible in a total body scan (TBS), in images that are more sharply focused and detailed than ever before. TBS is one of the central topics being discussed at the European Congress of Radiology (ECR 2007), an event held in Vienna (at Austria Center Vienna) from March 9 to 13, 2007, and attended by some 16,000 participants from 92 countries.


As University Professor Dr. Maximilian Reiser, director of the Institute for Clinical Radiology at the Ludwig-Maximilian University in Munich explained, "TBS has led to a complete change in paradigm in diagnostics. Previously, we doctors had to define our area of inquiry precisely in advance, for example, pain in the upper abdomen. Today, if we have any suspicions, we can check the entire body in an ultra-short time. That is a quantum leap forward, especially for systemic diseases whose effects can appear throughout the body."


"This advance has a variety of different applications, from life-saving uses to others whose value we should question," Professor Reiser added. The most important of these applications were presented at the European Congress of Radiology (ECR) 2007 in Vienna.


Polytrauma: After serious accidents in which several organ systems are, or at least might be, injured at the same time, a single examination shows bone fractures, spine injuries, cerebral haemorrhaging, puncturing of the lung, a pneumothorax, haemorrhaging in the pericardium or ruptures and haemorrhaging of inner organs. In short, everything that can quickly lead to death if not detected. Professor Reiser stated, "TBS increases not only a patient's survival rate but his quality of life. After all, complete rehabilitation often depends on correctly detecting injuries and beginning treatment within the first hour after the trauma."


Cancer Diagnosis: TBS makes it possible for the first time to detect any formations of metastases wherever they occur, making it an indispensable tool, especially in follow-up treatment to chemo- and radiation therapy.















Magnetic Resonance Angiography: In the event of arteriosclerosis, MRA enables the entire vascular system, including the heart, to be assessed, and thus the risk of stroke and cardiac infarction to be determined. It also brings to light infarctions that had previously gone undetected.


Psoriatic arthritis and other rheumatic diseases of the joints can be detected and completely diagnosed early on with TBS. Foci of inflammation can be detected even before the patient complains of them. Effective treatments, for example, with TNF inhibitors, can be started early in order to spare patients suffering and costs.


Virtual Autopsy: A growing number of people are refusing to approve an autopsy on family members, thus threatening the medical community with the loss of what is ultimately an important instrument for quality assurance. In combination with ultra-sound guided biopsies of key organs, a complete CT and MR scan of a corpse delivers information of a precision similar to a regular autopsy and of even greater precision when it comes to changes in bone marrow and connective tissue.


Nonetheless, just because a procedure is possible does not necessarily mean it is always sensible. Professor Reiser explained, "The prevailing view in the United States is that a whole-body MRA is indicated for anyone who can afford it. That implies high costs and simply invites the commercial exploitation of fear. I am not in favour of wholesale screenings, but I do advocate the examination of people with certain risk profiles, such as a genetic affliction or diabetes. We have taken this approach in Munich and used TBS to detect a significantly large number of vasoconstrictions in vessels supplying the brain and in leg arteries, which allowed us to treat them, I hope, in time."


About B&K KOMMUNIKATION


Press office for a number of scientific congresses, such as the Annual Meeting of the European Society of Neurology (ens)


B&K KOMMUNIKATION

Porzellangasse 35

bkkommunikation.at

GSK And BJD Collaborate On A New Educational Programme To Reduce Global Burden Of Joint Pain

The Bone and Joint Decade (BJD) international initiative and GlaxoSmithKline (GSK) announced the launch of the LIBERATE™ joint pain management programme during the BJD's World Conference in Lund, Sweden. The BJD, which is endorsed by the United Nation's World Health Organisation, and GSK have partnered to develop the global programme that provides information on practical and clinically proven techniques that people can use to self-manage their joint pain.


"Our vision is that the programme will motivate and enable people worldwide with joint pain to take an active role in their own care through the provision of education and information," said Professor Anthony Woolf, member of the BJD International Steering Committee, and rheumatologist from the Royal Cornwall Hospital in the UK.


The educational programme emphasises the importance of a holistic approach to joint pain management by focusing on six essential areas: diet, exercise, medications, mental attitude, tools and devices and alternative therapies. The programme provides ideas and techniques from medical experts that people with joint pain can immediately incorporate into their lives.


Musculoskeletal conditions, which include arthritis, are the leading cause of disability and time off work for sick leave around the world. Osteoarthritis is the most common form of arthritis and affects more than 135 million people worldwide. It is the fourth most frequent cause of health problems in women worldwide and the eighth in men.


"The incidence of musculoskeletal conditions, such as osteoarthritis, increases markedly from the age of 40 years. As the global population ages, the number of people with joint pain is expected to increase significantly. The aim of this programme is to show that there are simple ways to reduce joint pain, improve mobility, slow down the damage to joints, and enhance quality of life," stated Jacqueline Bain, a GSK global director of medical marketing.


The LIBERATE™ programme materials are currently written in English and will be translated into multiple languages throughout 2011.


Source: Glaxosmithkline

Disclosing Your Feelings May Help The Course Of Rheumatoid Arthritis: Results From A Randomized Clinical Trial

The health and physiological effects of an intervention which facilitates the opening of feelings are described in a paper published in the current issue of Psychotherapy and Psychosomatics.


The efficacy of emotional disclosure in alleviating psychological and physical stress has been well documented in controlled laboratory studies. A next step is to evaluate its clinical utility in 'real world' settings. A group of Dutch investigators adapted the emotional disclosure intervention for use in home-based settings by stimulating the suggested effective ingredients of cognitive-emotional processing, and evaluated its psychological and clinical effectiveness.


Reviews indicated the need to examine the physiological changes brought about by emotional disclosure, which may be particularly relevant in immune-mediated diseases. This study was the first to examine neuroendocrine and immune changes after emotional disclosure in patients with rheumatoid arthritis. Sixty-eight patients were randomly assigned to four weekly oral emotional disclosure or time management sessions.


At baseline and 1 week and 3 months after the sessions, depressed and cheerful mood, joint scores, erythrocyte sedimentation rate, cortisol, noradrenaline, interleukin-6 (IL-6), interferon- (IFN- ), and IL-10 were evaluated. Repeated measures analyses of variance were performed. At the end of the investigation, no effect on psychological well-being and clinical outcome was found (p 0.10). Cortisol (p = 0.01) and the serum level of the pro-inflammatory cytokine IFN- (p = 0.05) were differentially affected by the two conditions.


The change of IL-6 nearly reached significance (p = 0.07). The physiological changes are in agreement with theories on the mechanisms underlying emotional disclosure benefits and are suggestive of better disease control after emotional disclosure. General and study-specific reasons for the absence of psychological and clinical effects are discussed. The findings warn against widespread implementation of this home-based emotional disclosure intervention in unselected rheumatoid arthritis samples.


Source: Psychotherapy and Psychosomatics

Where Do New Therapies Work Best?

An observational study to investigate how new therapies for rheumatic diseases perform across different conditions has revealed that they may be more successful in certain conditions. The data is presented today at the Annual European Congress of Rheumatology in Amsterdam, the Netherlands. An increasing proportion of patients with rheumatic conditions such as ankylosing spondylitis (AS), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) now receive anti-TNF treatment - a newer group of drugs which are used to reduce inflammation and manage disease activity*. Study lead Dr Marte Heiberg, of the Dept of Rheumatology, Diakonhjemmet Hospital, Oslo, told delegates: "Many studies have focused on efficacy of these drugs, however less is known about comparative real life performance of these drugs across different diagnostic groups".



The study was conducted across 5 Norwegian Rheumatology Departments and included 796 RA patients, 162 PsA patients and 211 patients with a diagnosis of AS. All patients were on an anti-TNF treatment regimen of infliximab, etanercept or adalimumab +/- methotrexate (MTX). The primary outcome was the number of patients still on therapy at one year - known as the adherence to therapy. RA was used as the reference group and within each diagnostic group the adherence to anti-TNF monotherapy versus TNF+MTX was compared.



The relative risk for withdrawal from TNF+MTX versus anti-TNF monotherapy was 0.54 for RA patients, 0.49 for PsA patients and 0.83 for AS patients, demonstrating that combination treatment strategy of anti-TNF+MTX worked better than anti-TNF monotherapy in patients with RA and PsA. Although the crude one-year overall drug adherence rates for anti-TNF therapy were superior in patients with PsA and AS compared to RA, after adjusting for age, gender and concomitant MTX, the adherence to anti-TNF treatment were similar in patients with RA and PsA whereas the adherence to anti-TNF treatment was superior in patients with AS compared to RA.



Dr Heiberg stated: "This is a fresh insight into the performance of these very good treatment options and helps to build a greater picture of how they work across the different rheumatology disease areas. Whilst many of the anti-TNFs were originally used in RA, it is most interesting to note that they could actually work for a comparatively larger proportion of patients with an AS diagnosis."







Notes to editors



* Anti-TNFs are genetically engineered biological agents - to give them their full title 'biologic response modifiers'. They act by blocking the action of tumour necrosis factor (TNF) - a chemical believed to play an important role in causing the inflammation and tissue damage that occurs in rheumatoid arthritis. Anti-TNFs may be able to delay or even prevent this damage.
















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: eularpressofficeuk.cohnwolfe



Jim Baxter

Jo Spadaccino

Mia Gannedahl



ABSTRACT NUMBER: OP0091



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 7th Annual European Congress of Rheumatology in Amsterdam (EULAR 2006) 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: eular/



Contact: Mia Gannedahl



European League Against Rheumatism

Knee Replacement In Elderly Patients Shown To Improve Balance

Total knee replacement (TKR) successfully relieves pain and improves function in patients with advanced knee arthritis, according to a study presented today at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). The surgery also significantly improves dynamic balance among elderly patients.


Impaired balance and increased tendency to fall are common complaints among the elderly suffering from severe osteoarthritis (worn cartilage). The purpose of the study was to determine whether TKR had any effects on balance measures, in correlation with functional balance and quality of life. This is especially important because falls are the leading cause of injury for senior adults in the U.S., and hip fractures that result from falls can be lethal for elderly patients.


"Balance is critical to the elderly, especially those with knee problems. This study reinforced our hypothesis about how an osteoarthritic patient's function is compromised not only due to pain, but also by balance," said Leonid Kandel, MD, study author and orthopaedic surgeon, Department of Orthopaedic Surgery, Hadassah Mount Scopus Hospital, Jerusalem, Israel.


The study examined 63 patients, with a mean age of 73, who had total knee replacements and participated in follow-up evaluations after one year. The study measured accurately static and dynamic balance with a new computerized system called the Balance Master. The study found:


- Significant improvement in dynamic balance one year after surgery;


- Significant progress in balance-determined motor tests; and


- Strong statistical correlation between the balance and the Oxford Knee Score functional questionnaire and the quality of life questionnaire SF-36.


One year after surgery, the correlation between patients' improved balance and their ability to walk and perform daily activities was stronger than the correlation between their reduced pain and their ability to walk and do daily activities.


"We are learning that pain relief may not be the only benefit that improves function after knee replacement," explained Dr. Kandel. "This improved balance is a significant quality-of-life change in elderly patients."


Elderly individuals considering knee replacement should talk to their orthopaedic surgeon about the rehabilitation process and ways to improve balance following surgery. Other questions to consider prior to surgery can be found at orthoinfo.

Source
American Academy of Orthopaedic Surgeons

Cimzia(R) Study Shows Rapid Reduction Of Symptoms And Inhibition Of Joint Damage Progression In RA

UCB announced today the online publication of pivotal study results showing CIMZIA® (certolizumab pegol), the only PEGylated anti-TNF (Tumor Necrosis Factor) together with methotrexate (MTX) rapidly reduced symptoms of disease and inhibited progression of joint damage in adult patients with active rheumatoid arthritis (RA), with sustained results for up to one year. The RAPID (RA PreventIon of structural Damage) 1 study data is published in Arthritis & Rheumatism, the peer-reviewed journal of the American College of Rheumatology.



Both co-primary endpoints, which included the ACR20 responder rate at Week 24 and the change from baseline in the modified Total Sharp Score (mTSS) at Week 52, were met in the one-year study. Patients in both CIMZIA® together with MTX treatment arms were shown to have a significantly higher ACR20 response at 24 weeks (p

RAPID 1 and a simultaneous study, RAPID 2, are the first large, placebo-controlled Phase III trials demonstrating the efficacy and tolerability of CIMZIA® in the treatment of RA, as part of a clinical trials program involving more than 2,300 patients.



The most commonly reported serious adverse reactions were infections (including tuberculosis) and malignancies (including lymphoma). The most commonly reported adverse events were headache, nasopharyngitis, and upper respiratory tract infections. Pooled safety data from both studies showed that the incidence of injection site burning and stinging (n=

Inconclusive Results From Research Into Biologics-Associated Cancer Risk

Biologics-naive Juvenile Idiopathic Arthritis (JIA) patients may have an increased risk of cancer compared with the general Swedish population, according to research presented at EULAR 2010, the Annual Congress of the European League Against Rheumatism in Rome, Italy. Results of an additional study, which researched a small cohort of patients showed an increased frequency of cancer in those receiving the biologic etanercept, however, results were deemed not statistically significant by researchers.



The results of a population-based Swedish cohort study found that the incidence of cancer among paediatric patients with JIA identified during the last 40 years was comparable to that seen in the general population, (0.5 vs. 0.4 cases per 1000 person years, Relative Risk (RR)=1.1, 95%CI 0.9-1.5). Subset analyses however indicated that subjects diagnosed with JIA since 1987 (the year that the Swedish patient registry attained nationwide coverage) were at elevated risk of developing cancer (RR=2.3, 95%CI 1.2-4.4, 13 JIA cancers vs. 30 in comparator), attributed to an increased occurrence of cancers of the lymphatic system (RR=4.2, 95%CI 1.7-10.7, 8 cancers in JIA vs. 10 in comparator).



"These results are intriguing and suggest that in the past 20 years, patients with JIA not treated with biological therapies appear to have an elevated risk of cancer compared with the general population," said lead author of the study Dr. Julia Simard, Clinical Epidemiology Unit, Karolinska Institute, Stockholm, Sweden. "The results of our study indicate that evaluation of cancer risks with biologics in paediatric populations need to factor in differences in incidence of cancer between these patients and the general population. From a clinical point of view, it should be remembered that although we noted an increased risk in relative terms, the excess risks remain low in absolute terms."



The Swedish study assessed a national JIA cohort of 9,020 patients. For each JIA patient, up to five general-population comparators were identified (n=44,858). In the biologics-na??ve JIA cohort, 60 cancers were observed during 131,144 person-years compared to 266 cancers during 661,758 person-years in the population comparator. Researchers noted that sensitivity analyses did not reveal an explanation for the differences seen between patients identified before and after 1987.



The results of the second study combined data on 1,721 patients treated with etanercept from three prospective JIA registries in Germany, the UK and the US. Of the 1,641 patients who qualified for the primary analysis, two cancers were reported. Whilst this yielded a rate higher than expected when compared to the general population, it was not statistically significant (RR estimated using a Standardized Incident Ratio (SIR) of 3.7 (0.5-13.4, 95%CI)). This is believed to be in part due to the low event rate. The interpretation of these findings may be further limited by the fact that the comparator rates were based on a general population and not a biologics-na??ve JIA population, as per the Swedish study, which suggests this may indicate an increased underlying risk of cancer.



Abstract Numbers: OP0086 & OP0274



Source:

Caroline Butt

European League Against Rheumatism

Higher Prevalence Of Periodontal Disease In Rheumatoid Arthritis Patients

Over 1.3 million Americans suffer from rheumatoid arthritis (RA), a chronic, inflammatory disease of the joints. RA is a disabling condition, and can lead to long-term joint damage resulting in persistent pain and loss of function in affected areas. A recent study published in the June issue of the Journal of Periodontology, the official publication of the American Academy of Periodontology (AAP), uncovered yet another potential side effect of RA. Researchers in Berlin, Germany discovered that patients with RA have a higher incidence of periodontal disease compared to healthy controls.



For some patients, adverse RA symptoms may affect manual dexterity, which can make one's daily routine quite difficult. One area that may be affected is oral hygiene which can ultimately lead to periodontal disease. However, these research findings indicate that poor oral hygiene alone did not account for the association between RA and gum disease, suggesting that other factors may play a role as well.



The study examined the oral health of 57 RA patients and 52 healthy controls. To determine oral hygiene status, each participant underwent a comprehensive oral examination including an assessment of plaque accumulation and gingival inflammation, both indicators of oral hygiene. Probing pocket depth and clinical attachment loss, two markers of periodontal disease, were also measured. Researchers used questionnaires to gauge the subjects' risk factors for periodontal disease.



The study findings indicated that RA patients were nearly eight times more likely to have periodontal disease compared to the control subjects. These findings accounted for demographic and lifestyle characteristics such as age, gender, education and tobacco use. Researchers then examined the extent to which poor oral hygiene was connected to the increased occurrence of gum disease in RA patients. The results showed that while oral hygiene was markedly a factor, it did not fully explain the association between the two diseases, suggesting that there may be other parameters responsible for the increased prevalence of gum disease in RA sufferers.



"With results suggesting that rheumatoid arthritis is associated with periodontal disease, it is easy to assume that an RA sufferer is perhaps unable to properly care for his or her teeth and gums due to the debilitating nature of the disease," says Dr. Kenneth Kornman, editor of the Journal of the Periodontology. "However, this study implies that there are other potential factors involved. For instance, both RA and gum disease are systemic inflammatory disorders which may explain the connection between the two. Inflammation is already thought to link periodontal disease with other conditions such as cardiovascular disease and diabetes. We look forward to future research that may reveal the biological mechanisms that link these two important diseases."



In an effort to best maintain oral health, RA patients are encouraged to brush and floss on a regular basis and see a dental professional twice a year. If gum disease develops, consulting a periodontist is an effective way to determine the most appropriate course of treatment.



According to Dr. Susan Karabin, President of the AAP, maintaining the complete health of RA patients should be a collaborative effort. "It is critical that dental professionals and medical professionals work together when treating a patient living with rheumatoid arthritis. This partnership will assure that both the oral and overall health of these patients is paramount."







To learn more about gum disease, locate a periodontist, or to find out if you are at risk for periodontal diseases, visit perio/.



About the AAP



The American Academy of Periodontology is an 8,000-member association of dental professionals specializing in the prevention, diagnosis and treatment of diseases affecting the gums and supporting structures of the teeth and in the placement and maintenance of dental implants. Periodontics is one of nine dental specialties recognized by the American Dental Association.



Source: Meg Dempsey


American Academy of Periodontology

Improving The Standard Of Rheumatology Care In Europe

The Annual European Congress of Rheumatology commenced today with a comprehensive set of recommendations which aim to clarify treatment options for a range of debilitating rheumatic conditions. Following a rigorous development process involving numerous multidisciplinary experts across Europe, recommendations for the management of hand osteoarthritis, systemic lupus erythematosus (SLE) and fibromyalgia have been proposed for endorsement by EULAR (The European League Against Rheumatism), along with recommendations for conducting clinical trials in SLE and systemic vasculitis.



Professor Tore Kvien, EULAR president, stated: "The EULAR executive place great importance on the need to provide recommendations regarding management strategies for rheumatic diseases in order to encourage the best standard of care across the whole continent. The processes we require for endorsement are based on strict criteria and rely on the best available evidence".



EULAR will consider a range of research initiatives under its endorsement programme, which is led by the EULAR standing committees and governed by a set of published standardised operating procedures1. Topics include management of musculoskeletal disorders, conducting clinical trials, use of specific tools (e.g. bone densitometry, ultrasonography) and even classification or diagnostic criteria. Recommendations already endorsed by EULAR in recent years include management considerations for knee osteoarthritis, hip osteoarthritis, ankylosing spondylitis, early arthritis and the management and diagnosis of gout.



Professor Maxime Dougados, MD, Professor of Rheumatology at the Universite Rene Descartes, Paris and Chair of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials, said that the latest recommendations were accepted for consideration by EULAR for a variety of reasons, but that all were very relevant issues in daily practice and would be of great value to European health care professionals and, ultimately, for patients. He said: "For a disease such as lupus it is evident that many different physicians are involved in treating these patients and this may inevitably lead to variety in practice. In other areas such as fibromyalgia, which has a relatively high prevalence at 4% of the population, the strength of evidence is perhaps not as robust as it could be. Whether pharmacological or non-pharmacological intervention is involved, in all of these areas there is a clear need for reinforcement of best practice, including simple guidance on effective treatment, which can be easily accessed by busy professionals".



All current recommendations will be presented at the opening session of the EULAR scientific programme on Wednesday 21st June in the State-of-the-Art/Best Practice stream. The EULAR standing committee is expected to ratify the recommendations by end of June 2006.



















Reference

1. Dougados M et al. EULAR standardised operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees. Ann Rheum Dis. 2004 Sep;63(9):1172-6



For further information about this story, or to request an interview with one of the abstract leads or a EULAR representative, please do not hesitate to contact the EULAR congress press office on:-



Email: eularpressofficeuk.cohnwolfe



Jim Baxter

Jo Spadaccino

Mia Gannedahl



Abstract numbers: SP0002, SP0003, SP0004, SP0005



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 7th Annual European Congress of Rheumatology in Amsterdam (EULAR 2006) 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: eular/



Contact: Mia Gannedahl



European League Against Rheumatism

Decline In Work Disability Due To Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the joints and, in severe cases, vital organs. Marked by pain, fatigue, and loss of dexterity and mobility, RA has been strongly associated with work disability in the US. In previous studies of patients with advanced RA, 10 years in duration, the prevalence of work disability has been estimated at as high as 50 percent. However, most studies examining this costly effect of RA are well over a decade old. Since then, much has changed about the disease and the nature of work.



Prompted by these changes, researchers at Boston University speculated that the high prevalence of work disability among RA patients may have changed, and they set out to provide a comprehensive, up-to-date estimate. Featured in the April 2008 issue of Arthritis Care & Research (interscience.wiley/journal/arthritis), their data suggests that the employability outlook for men and women with advanced RA has improved since the mid-1980s.



Using the National Data Bank (NDB) longitudinal study of RA, researchers identified 5,384 subjects for analyses. All participants completed extensive surveys every 6 months between January 2002 and December 2005. Questions covered employment status at disease onset, discontinuation of work prior to traditional retirement age - 65 years, cessation of work attributed to arthritis, and, for those currently employed, work characteristics. Participants were also asked to supply demographic data and the date of RA diagnosis. Functional limitation was determined by score on the Health Assessment Questionnaire (HAQ). Subgroups of patients were formed to assess prevalence of work disability by 5-year intervals of disease duration. In addition, the annual incidence of work disability was calculated over 3 separate time periods: 2003, 2004, and 2005.



The mean age of the RA study population was 52 years. 82 percent of the subjects were women and 63 percent had more than a high school education. The mean disease duration was 14 years and the mean HAQ score was 1.0, indicating moderate functional limitation. 85 percent of subjects had been employed at disease onset and 56 percent were currently employed. Nearly three-quarters of these employed subjects worked full-time, 41 percent held professional or managerial jobs, and 16 percent were self-employed. Among subjects who were not employed, 43.5 percent were disabled; the remainder described themselves as either retired, full-time homemakers, or unemployed.



The prevalence of work cessation before age 65 increased with years of disease duration. This ranged from 23 percent among patients with relatively early RA - 1 to 3 years, to 35 percent in those living with RA for a decade, and 51 percent in those with RA for at least a quarter century. The prevalence of arthritis-attributed work cessation also increased with disease duration but was somewhat lower, beginning with 14 percent in subjects with 1 to 3 years, increasing to 29 percent in subjects with 10 years, and culminating at 42 percent in those with RA for 25 years or more. The annual incidence of premature work cessation was 12 percent in 2003, 9 percent in 2004, and 9 percent in 2005. Incidence of work cessation directly attributed to arthritis was even lower, about 6 percent per year, and decreased slightly over the 3 years. 39 percent of the subjects who stopped working later returned to work over the course of the study period.
















Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, this study suggests a decline in the prevalence of RA work disability, particularly among patients with 10 years of disease duration, since the mid-1980s. As its authors note, there are several possible explanations for this, including declines in both the unemployment rate and the physical demands of jobs in the US, as well as improvements in the treatment of RA. Among other notable findings, many cases of work disability were temporary and many may have had little relationship to RA.



"Work disability among persons with RA in the US is still a substantial problem," observes the study's lead author Saralynn Allaire, ScD. "However, our data in comparison with previous US studies also suggest there has been some improvement over the past 15 to 20 years in those with longer-standing disease." As Allaire acknowledges, this study has limitations. "Because subjects with mild RA may not be fully represented in the NDB sample and may have less work disability, the actual RA work disability prevalence could be lower than we found. On the other hand, because NDB subjects have higher educational attainment and are more often white than the US population, and because these characteristics offer employment advantages, the actual RA work disability rate may be higher than we found."







Source: Sean Wagner


Wiley-Blackwell

Penn researchers add more evidence to demonstrate role of COX inhibitors in heart-disease risk

In two articles, published in Circulation, researchers from the University of Pennsylvania School of Medicine provide
further evidence for the role of cyclooxygenases (COX) in heart-disease risk. In one, a statistical meta-analysis of two
placebo-controlled trials, the COX-2 inhibitor Bextra elevated the combined incidence of heart attack and stroke three-fold
in coronary artery bypass graft (CABG) surgery patients. In the second, the investigators found that a fat produced by COX-1
speeds hardening of the arteries in a mouse model of atherosclerosis, which may have implications for low-dose aspirin
therapy in heart patients.


Six years ago Garret FitzGerald, MD, Director of the Institute for Translational Medicine and Therapeutics at Penn, raised
the possibility that selective COX-2 inhibitors might predispose patients otherwise at risk for an increased incidence of
heart attack and stroke. This proposal was based initially on his studies of how celecoxib (Celebrex) and rofeocoxib (Vioxx)
worked in human volunteers.


The first unequivocal evidence of this risk emerged with the Merck-sponsored APPROVe study of Vioxx, leading to withdrawal of
the drug in September 2004. Evidence implicating a second member of the class, valdecoxib (Bextra) was presented by
FitzGerald in a lecture at the American Heart Association (AHA) in November 2004. This work - a collaboration led by Curt
Furberg of Wake Forrest University, along with Bruce Psaty of the University of Washington and FitzGerald - appears online
January 17 in Circulation and in the January 25th print edition of the journal.


In this first study, the researchers used a conventional statistical approach called meta-analysis to combine the findings of
two trials to obtain a stronger estimate of the risk of heart attack plus stroke than is possible from looking at either
trial alone. Their analysis suggests that the COX-2 inhibitor Bextra elevated the combined incidence of heart attack and
stroke three-fold in the study population of CABG patients.


Two placebo-controlled trials of Bextra and parecoxib (Dynastat) were performed in patients undergoing coronary artery bypass
graft surgery. These studies were sponsored by Pfizer, Inc. In both cases, intravenous Dynastat, which is converted to Bextra
within minutes in the body, was given before oral dosing with Bextra. The first involved roughly 400 patients and dosing
lasted 14 days. Concern was prompted by an apparent cardiovascular signal and the FDA did not grant approval to Dynastat,
despite clear evidence of pain relief from the Dynastat/Bextra combination compared to placebo. A second, larger study was
performed in which the dose of Bextra was reduced, as was the dosing period to 10 days. The figures from this study are now
incorporated in a revised drug label for Bextra available at the FDA website (fda).















This result is consistent with the original mechanism proposed by FitzGerald in 1999 that COX-2 inhibitors may be problematic
for those at risk for heart disease. COX-2 is the main source of a fat - prostacyclin or PGI2 - which protects the heart from
factors that activate the clotting system, harden the arteries, and raise blood pressure. "Although a clinical trial is a
crude detection system for uncommon side effects, such as the cardiovascular risk from coxibs, we predicted that a signal
would be detected faster and in smaller studies in patients with activated clotting systems," says FitzGerald. "It is well
known that this is true of coronary artery bypass graft surgery patients." Studies of sufficient size and duration to detect
the expected rates of cardiovascular events in arthritis patients have not been performed with Bextra.


While FitzGerald stresses that the emergence of a cardiovascular signal with a second COX-2 inhibitor rendered the argument
for a class effect of the risk "compelling," the early cessation of a placebo-controlled trial of celecoxib (Celebrex) in
December 2004 by the National Cancer Institute (because of an excess incidence of heart attack and stroke) appeared to put
the matter beyond dispute.


A related paper from the FitzGerald group also appears online in the same issue of Circulation. Karine Egan, PhD, a
postdoctoral researcher in the FitzGerald lab, and colleagues at Penn and the Wistar Institute studied mice genetically prone
to hardening of the arteries (atherosclerosis) and showed that another fat - thromboxane or TxA2, this time produced by COX-1
- accelerates atherosclerosis. Indeed, they showed a drug that blocks TxA2 slowed this process at its early stages, although
it seemed ineffective once atherosclerosis was well established. "This is of particular interest, as low-dose aspirin
prevents heart attack and stroke by blocking COX-1 formation of TxA2 in blood cells called platelets," says FitzGerald. "Its
effects or those of a TxA2 blocker on hardening of the arteries has never been studied well in humans."


Egan and colleagues failed to detect a benefit from COX-2 inhibition in the atherosclerosis-prone mice, but they reasoned
that a potential benefit might be masked by the effect of the drug. Although platelet COX-1 is the major source of TxA2, this
fat can also be formed by COX-2 in cells called macrophages that invade the hardening vessel wall. Given what they had seen
with the TxA2 blocker, FitzGerald's group figured that they might need to add the TxA2 blocker to see the anti-inflammatory
benefit of the COX-2 inhibitor.


Adding the COX-2 inhibitor not only failed to add to the beneficial effects of the TxA2 blocker, it caused disturbing changes
in the makeup of the atherosclerotic plaques. "We were amazed," states Egan. "Addition of the COX-2 inhibitor caused changes
that, if they occurred in humans, would result in a loss of stability of the plaque, making it more likely to rupture and
activate clotting, causing heart attack or stroke."


"We must always be cautious projecting the results of studies in mice to clinical outcomes in humans," says FitzGerald.
"While low-dose aspirin works by switching off TxA2, a TxA2 blocker might act in subtle, but importantly different ways.
However, in so far as it mimics the effects of low-dose aspirin, these results would have disturbing implications for
patients at high cardiovascular risk treated with aspirin and a coxib."


FitzGerald adds: "The clear emergence of a cardiovascular hazard from COX-2 inhibitors in patients, the weak rationale for a
study of their protective properties in the first instance, and now this evidence from mice would indicate to me that a trial
in high-risk patients, such as that proposed for Celebrex is, at best, ill advised."


This paper was funded in part by grants from the National Institutes of Health, Servier Laboratories, and Merck Research
Laboratories. Servier and Merck had no influence on the design or interpretation of the studies, and the authors have no
competing financial interests.


This release can also be found at: uphs.upenn/news.


PENN Medicine is a $2.7 billion enterprise dedicated to the related missions of medical education, biomedical research, and
high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as
the nation's first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation's first
integrated academic health system).


Penn's School of Medicine is ranked #3 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S.
News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700
students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of
physician-scientists and leaders of academic medicine.


The University of Pennsylvania Health System includes three owned hospitals [Hospital of the University of Pennsylvania,
which is consistently ranked one of the nation's few "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania
Hospital, the nation's first hospital; and Presbyterian Medical Center]; a faculty practice plan; a primary-care provider
network; two multispecialty satellite facilities; and home care and hospice.


Karen Kreeger

karen.kreegeruphs.upenn

University of Pennsylvania Medical Center


View drug information on Bextra; Vioxx.

Rheumatoid Arthritis, Role Of Type II Collagen, Study

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints, which gradually erodes the cartilage and bone. The agents of destruction include inflammatory cells, cytokines, and protein-degrading enzymes known as matrix metalloproteinases (MMPs).

The vicious cycle begins when inflammatory cells infiltrate the tissue lining the joints and consume excess oxygen. In addition to unleashing MMPs, the oxidative stress provokes non-enzymatic glycation - a chemical binding of sugar molecules and proteins. Telltale signs of glycation have been found in blood, urine, and synovial fluid of RA patients.


The primary protein in cartilage, Type II Collagen (CII) is crucial to joint health and function. Yet, the involvement of CII in the process of joint inflammation has proven difficult to substantiate. To gain a clearer understanding of CII's role in the pathogenesis of RA, researchers at Queen Mary, University of London and others studied its behavior within an inflamed joint, when modified by oxidants linked to inflammation or by ribose, a five-carbon sugar common to all living cells.


Featured in the December 2005 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), their findings support CII's potential contribution to antibody binding and RA's devastating progression.


For their investigation, the researchers collected blood serum samples from 31 RA patients. Between the ages of 65 to 93 years, the patients had disease in varying stages and were receiving different treatments. For control purposes, serum samples were also collected from 41 patients with other inflammatory joint diseases, including osteoarthritis and lupus, as well as back pain, osteoporosis, and gout. Both RA and non-RA samples were analyzed for their ability to bind to pure and natural CII, obtained from bovine cartilage, and to CII that had been chemically modified.


The modified CII included three oxidants present in the rheumatic joint - hydroxyl radical, hypochlorous acid, and peroxynitrite - and ribose. The results were evaluated by a state-of-the-art 3-D fluorescent profile, followed by enzyme-linked immunosorbant assay (ELISA) and Western blotting.


Of the 31 RA serum samples analyzed, only 3 showed antibody binding to natural CII - affirming this protein as an innocent bystander in autoimmunity and its inflammatory toll on the joints.


However, the percentage of samples that exhibited antibody binding increased 4-fold when tested with modified CII. In fact, 45 percent of all RA samples were assessed with moderate to strong antibody binding reactions. CII treated with hypochlorous acid was the most reactive, followed by CII treated with peroxynitrite, glycation, and hydroxyl radical, respectively. In contrast, only 1 non-RA sample showed strong antibody binding to modified CII.


"The present findings support the possibility that chemical modification of self antigens, in RA in particular and in inflammation in general, is the cause of formation of neoepitopes," reflects the study's leading author, Ahuva Nissim, Ph.D. "We propose that the oxidative modification of CII creates a CII autoantigen."


This hypothesis has important implications for the further study and enhanced understanding of the pathology of RA - a complex autoimmune disease.


Article: "Generation of Neoantigenic Epitopes After Posttranslational Modification of Type II Collagen by Factors Present Within the Inflamed Joint," Ahuva Nissim, Paul G. Winyard, Valerie Corrigall, Rewas Fatah, David Perrett, Gabriel Panayi, and Yuti Chernajovsky, Arthritis & Rheumatism, December 2005; 52:12; pp. 3829-3838.


John Wiley & Sons, Inc.

interscience.wiley


Help us complete a Work and Well Being Survey that is Collaborating in. We are getting no financial remuneration for this project:
Click Here to Go to the Survey

Chronic Disease Keeping Older Australians Out Of The Workforce

Chronic diseases such as diabetes and arthritis may render more than 660,000 older Australians unable to work, a retrospective analysis has found, prompting calls for the government to address workers' health concerns if it wants to boost the workforce.


Director of Research at the Northern Rivers University Department of Rural Health, Associate Professor Deborah Schofield and colleagues analysed data from the Australian Bureau of Statistics to identify conditions associated with non-participation in the labour force by Australians aged 45-64 years.


Their study, published in the latest issue of The Medical Journal of Australia (MJA), estimated that 663,235 older Australian workers were missing from the labour force because of ill health in 2003, reducing Australia's gross domestic product by around $14.7 billion per annum.


"Back injuries, arthritis and mental health disorders accounted for approximately half the missing workers," Dr Schofield said.


Other long-term health conditions associated with being out of the labour force were nervous system diseases, heart disease, diabetes, and asthma.


"In the past, government policy has focused on economic incentives to increase employment of older people," Dr Schofield said.


"For example, an Age Discrimination Bill was passed and the 15 per cent tax on lump sums and pensions from superannuation schemes after the age of 60 years was removed.


"However, these economic measures have not addressed the health conditions associated with much of the low labour force participation of older workers, and are unlikely to have a major impact on the labour force participation of people who are ill."


Dr Schofield and colleagues suggest the government should actively seek to turn around the rise in Australia of obesity - a risk factor for numerous chronic conditions. Treatment of mental illness, such as depression, is also important.


"With emerging skill shortages and an ageing workforce, Australia needs a more holistic approach to increase labour force participation among older people that considers the interaction of health, illness prevention and labour force priorities."


Medical Journal of Australia

mja.au

UD Awarded $11M For Osteoarthritis Research And Unique Mentoring Program For Women Scientists

The University of Delaware has been awarded $11 million from the National Institutes of Health for leading-edge, "translational" research on osteoarthritis that includes a unique mentoring program to foster the development of women biomedical researchers at UD.



The grant, led by Thomas Buchanan, professor and chairperson of the Department of Mechanical Engineering, is the second five-year award to UD's Center for Biomedical Engineering Research from NIH's Centers of Biomedical Research Excellence Program. The center received a $6.4 million grant in 2002.



The wearing down of cartilage, the natural cushion between the bones and joints, causes osteoarthritis, the most common form of arthritis. The disease typically affects the knees, hips, back and hands.



According to Buchanan, the latest grant will enable UD to continue building the infrastructure and expertise to address the mechanisms of osteoarthritis, its prevention and treatment by examining the disease from the integrated perspectives of tissue mechanics, biomechanics, physical therapy and clinical intervention.



The program will involve 14 faculty in three of UD's seven colleges, including the departments of biological sciences and physical therapy in the College of Arts and Sciences, mechanical engineering in the College of Engineering, and health, nutrition and exercise sciences in the College of Health Sciences. Researchers from Alfred I. duPont Hospital for Children and the Kessler Medical Rehabilitation Research and Education Corporation will serve as collaborators.



"What we have at UD that's really unique is a collection of people to address osteoarthritis across multiple levels, which is what translational medicine is all about," Buchanan said.



"We have people who can look at the proteins that are important to the healing of cartilage, for example, to people who can create biomechanical models showing the movement of bones and joints, to people who can conduct the clinical studies critical to the development of therapies. We can span lots of disciplines, which is what's exciting here," he noted.



Buchanan said the program's focus on mentoring women in science and engineering evolved after the request for research proposals was circulated at UD. Women faculty submitted the top-five research proposals.



"We wanted to find ways to use this program as an opportunity to promote their role," he noted.



Nationally, women continue to be underrepresented in the academic ranks of science, technology, engineering and mathematics. At UD, the percentages of all tenured/tenure-track women faculty are 17 percent in the natural sciences and 10 percent in engineering, according to Buchanan.
















"Mechanical engineering, for example, traditionally has been a male discipline although many of our new faculty are women," Buchanan said of the UD department he chairs. "Our goal is to find good faculty mentors and start working with these new hires to see the discipline change. We need better mentoring to help with the process."



The grant's chief components, Buchanan said, are to create a core facility for mentoring women in science and engineering, to establish a new lab focusing on cytomechanics, or cell mechanics, and to advance five integrated research projects in osteoarthritis.



L. Pamela Cook, professor of mathematical sciences, associate dean of engineering and chairperson of UD's Commission on the Status of Women, is assisting with the development of a strong internal networking and support system for women faculty in science and engineering. Professional development workshops, establishment of a faculty ombudswoman and University-wide presentations on gender issues, including promotion and tenure, are being planned.



Women faculty are directing the grant's five research projects. Two are led by senior faculty, who also are helping to mentor the junior faculty in charge of the remaining projects.



Mary C. Farach-Carson, professor of biological sciences and director of UD's Center for Translational Cancer Research, and Catherine Kirn-Safran, research assistant professor of biological sciences, are leading a team to define the structural and functional roles of the biomolecule perlecan in cartilage biology. The biomolecule's heparan sulfate chains are believed to be critical to the maintenance of cartilage in adults and the regrowth of damaged cartilage.



Liyun Wang, assistant professor of mechanical engineering, is exploring the pathway of communication between bone and cartilage. Experiments have shown that bone cells from osteoarthritic patients can cause cartilage to break down. Wang is combining lab techniques with mathematical modeling to characterize the movement of molecules through bones in normal and osteoarthritic joints.



Lynn Snyder-Mackler, Alumni Distinguished Professor of Physical Therapy and director of the Graduate Program in Biomechanics and Movement Sciences at UD, is leading a research team to determine if rehabilitation that normalizes quadriceps strength between the limbs after total knee replacement--one of the most common surgeries in the U.S.-- will ultimately decrease the progression of osteoarthritis of the hip and knee.



Jill Higginson, assistant professor of mechanical engineering, is investigating the muscle forces and coordination strategies used during walking in individuals with age-related osteoarthritis of the knee. A combination of MRI, gait analysis, electromyography and biomechanical modeling and simulation will be employed to determine the most effective nonsurgical interventions.



Katherine Rudolph, assistant professor of physical therapy, is working to understand how quadriceps strength, knee stiffness, proprioception and instability contribute to osteoarthritis of the knee. The study will help researchers understand the strategies that can be used to improve knee function without further joint damage and aid in developing screening tools to identify patients who will benefit from rehabilitation programs.






Contact: Tracey Bryant


University of Delaware