Annex 6.2.2
Current and ongoing research and recommendations from experts and
organizations
Organization/expert
committee/ author
AAOS
American Academy of
Orthopaedic Surgeons 1
Research Areas and recommendations on direction of OA research
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Mayo Clinic 2
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National Institute of
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Explore the genetic, biological and mechanical factors that influence the
progression of arthritis
Examine the molecular basis of osteoarthritis, biological repair processes
and bioengineering approaches to tissue regeneration with special
emphasis on cartilage repair
Study the interaction of materials and wear and, specifically, the
interaction of the material with the host, emphasizing early detection
methodologies, prevention and medical intervention.
Examine the effect on tissues of debris particles and investigate possible
molecular markers of loosening and osteolysis.
Explore the effectiveness of alternative therapies in reducing symptoms
of osteoarthritis.
Study the short- and long-term effects of alternative bearing surfaces.
Evaluate new coatings and methods of implant fixation, including use of
bioactive materials.
Explore the benefits of chondral transplantation in preventing
degeneration of joints.
Study joint kinematics around the hip, ankle, elbow, shoulder, wrist and
knee in normal, arthritic and reconstructed states with the development
of high-speed computational methodologies to stimulate natural and
artificial joint performance.
Explore the role of novel imaging technologies on joint arthroplasty,
including RSA, DEXA, surgical navigation, minimally invasive and
robotic surgery.
Expand the use of finite element analysis (FEA) to predict implant
performance, identify fundamental mechanisms of failure and predict
performance failure of mechanical devices.
Apply basic principles for the mechanics of materials to individual
connective tissue cells to define the cell response to mechanical stimuli
and the cellular pathways involved on the transduction of mechanical
inputs.
Implement new strategies to minimize technical complications, such as
dislocation in total hip replacement and arthrofibrosis in total knee
replacement, and medical complications, such as infection, venous
thrombosis and embolism.
Develop new arthroplasties such as ankles, first metacarpal-phalangeal
and wrist.
Study the relationship between quality and volume in total joint
arthroplasty.
Study the apparent underutilization of total joint arthroplasty in some
geographic areas and among some ethnic groups.
There is a growing body of evidence that complementary medicines may
have a role in managing OA. However mainstream scientific methods are
not available to evaluate the effectiveness and safety of complementary
medicines
Further research is required into the effects in the following areas:
 Nutritional supplements such as glucosamine; glucosamine +
chondroitin; glucosamine + chondroitin + manganese
 Complementary and alternative treatments such as acupuncture,
copper, homeopathy and magnets
NIAMS has included a very detailed and thorough section on the
6.2.2-1
Annex 6.2.2
Organization/expert
committee/ author
Health (NIH)
National Institute of
Arthritis and
Musculoskeletal and
Skin Diseases (NIAMS)
Research Areas and recommendations on direction of OA research
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ongoing osteoarthritis initiative.
An extensive appendix of US longitudinal studies of osteoarthritis are
listed
None of the studies involve drug research and development at the
current time.
3
Arthritis FoundationArthritis Foundation
Research4, 5.
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The arthritis Foundation is currently funding 68 studies focuses on OA.
Specific research areas include: genetics; biochemical factors growth
factors; studying vitamins and supplements; promoting active life;
promoting better surgical outcomes and preventing work disability.
Physicians conducting the study, names of the institution and brief
description of the studies are provided by the Organization.
Treatment Advances
Knowledge in the development and progression of OA has resulted in a
number of new approaches to treatment. Recent advances and experimental
treatments include:
 Development of a new class of anti-inflammatory drugs called COX-2
inhibitors. Additional COX-2 drugs are in clinical trials. A novel agent
that not only blocks both COX enzymes, but also inhibits another proinflammatory enzyme called lipoxygenase, has also shown promising
results in early trials.
 Chondroprotective agents are being studied. These agents protect
cartilage from further breakdown and could play an important role in
early disease prevention or help in slowing down joint damage and
perhaps even reverse the disease by stimulating cartilage growth.
 Researchers are also testing a type of gene therapy in which genetically
altered cells are injected into the joint to block cartilage breakdown.
Preliminary results in animal studies have shown success in slowing
down the progression of OA.
 Developments in the areas of “tissue engineering” are providing
therapeutic options for those who already have irreparable cartilage and
joint damage. One approach being tested is to replace damaged cartilage
with stem cells (cells capable of making new cartilage cells) taken from a
person's healthy knee cartilage, from bone marrow, and even from fat
harvested from liposuction.
 Patients with significant pain and disability, total joint replacement using
new reconstructive surgical techniques and more durable implant
materials may provide an alternative option and could have the
potentional to improve function.
Studying Vitamins and Supplements
Arthritis Foundation researchers are providing some insights about the
effects of some commonly used vitamins and supplements. For instance:
 Exploring if and how glucosamine is an effective chondroprotective
agent.
 It has been discovered that that vitamin C increases the production of
cartilage proteins, such as collagen and aggrecan, but high doses actually
worsened OA in guinea pigs. Studies are being conducted on how to
maximize the use of vitamin C to protect cartilage.
Using Growth Factors
Many ongoing studies funded by the Arthritis Foundation are focused on
6.2.2-2
Annex 6.2.2
Organization/expert
committee/ author
Research Areas and recommendations on direction of OA research
understanding and testing the use of various growth factors that can
stimulate the production of cartilage cells and proteins. Growth factors may
be appropriate targets for preventing cartilage damage as well as for
repairing cartilage that is already damaged. For instance:
 Bone morphogenic protein (BMP) growth factors can be used to signal
immature "stem cells" from the bone marrow to differentiate into bone or
cartilage cells.
 Studies on the regulation of insulin-like growth factor, which plays a key
role in maintaining healthy cartilage.
 Studies on gene therapy with BMP-7 to prevent cartilage damage.
 Studies on how a growth factor called vascular endothelial growth factor
(VEGF) may contribute to the early death of cartilage cells. Anti-VEGF
agents are already in clinical trials for treating certain types of cancer and
rheumatoid arthritis and may be useful in preventing cartilage damage
EULAR research
agenda based on expert
opinion on the
committee 6
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Bone and Joint Decade
2000-2010 (BJD) 7, 8, 9
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What can we do about
osteoarthritis.
Lohmander S 10
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Clinical predictors of response to pharmacological and
nonpharmacological interventions need to be determined
Establish uniform set of recommendation for uniform and full reporting
of clinical trails in OA
Studies should include quality of life and function as well as pain
outcome measures
Develop new imaging techniques for the diagnosis and follow up of OA
RCTs should assess nonpharmacological interventions
Determine the efficacy and safety of long term cox- inhibition on tissue
Examine the efficacy and cost utility of surgical treatments.
BJD was launched by the WHO in 2000
The campaign is coordinated by an international steering committee of
professional an patient representatives
Priorities- ‘to improve the heath-related quality of life of people with
bone and joint disease world wide by raising awareness and
understanding of these conditions and increasing the amount of research
funding’
A recent article on the developments of BJD concludes that the most
important research priority for musculoskeletal disease (with OA being
the biggest contributor) should be to strengthen evidence-based medicine
by closing the gap between clinical disease oriented research and
molecular research.
To help close this gap the following directions have been suggested:
 Encourage interactions between different research areas which will
provide openings for the development of new treatments of disease
 Assess the burden of disease and risk factors, in order to optimize
disease prevention and treatment outcomes
 Identify pathogenic molecular interactions in a relevant context
 Identify disease-regulating genes
 Develop an understanding of the roles of proteins in tissue
formation, function and cell behaviour
 Develop new targeted therapy based on an understand of molecular
mechanism in tissue turnover
 Develop tissue-engineered repair systems
Continue to study and clarify the genetics and epidemiology of OA
Examine the environmental risk actors and their interaction with genetic
background to assist in disease prevention
6.2.2-3
Annex 6.2.2
Organization/expert
committee/ author
Research Areas and recommendations on direction of OA research
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Continue studies to identify those who at risk for progression and severe
disease
Determine the molecular processes that are important for joint damage
Identify degradative agents that affect cartilage protection.
Determine if saving the cartilage will improve patient pain and function
Examine the role of local inflammatory processes in OA
Identify more effective outcome measures which can assist t in
accelerated testing and development of treatments
References to Annex 6.3.2:
http://www.aaos.org/wordhtml/bulletin/aug03/acdnws7.htm. AAOS American Academy of
Orthopaedic Surgeons. Last accessed 2004-02-19.
1
2
http://www.mayoclinic.com. Mayo Clinic. Last accessed 2004-02-19.
http://www.niams.nih.gov/ne/oi/oaepipappen_a.htm National Institute of Health (NIH)-National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Last accessed 2004-02-19.
3
4
http://www.arthritis.org/research/research_program/Osteoarthritis/default.asp,
Foundation-Arthritis Foundation Research. Last accessed 2004-02-25.
Arthritis
http://www.arthritis.org/research/research_program/Osteoarthritis/treatment.asp
Foundation-Arthritis Foundation Research. Last accessed 2004-02-25.
Arthritis
5
Jordan KM, Arden NK, Doherty M, Bannwarth B, et al. EULAR Recommendations 2003: An
Evidence Based Approach to the Management of Knee Osteoarthritis: Report of a Task Force of the
Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann
Rheum Dis. 2003; 62:1145-1155.
6
Lidgren L. The Bone and Joint Decade 2000-2010. Editorial. Bone and Joint Decade 2000-2010.
Bulletin of the World Health Organization 2003, 81 (9): 629.
7
Heinegard D, Lidgren L. Recent Developments and Future Research in the Bone and Joint Decade
2000. Perspectives-Bone and Joint Decade 2000-2010. Bulletin of the World Health Organization 2003,
81 (9): 686-688.
8
9
http://www.bonejointdecade.org. Bone and Joint Decade 2000-2010. Last accessed 2004-02-19.
10
Lohmander SL. What can we do about osteoarthritis. Arthritis Res. 2000; 2 (2):95-100.
6.2.2-4