Chondroprotective Agents
The expanding knowledge of articular cartilage biochemistry and pathogenesis
of osteoarthritis has focused research on slowing the progression of
degeneration and promoting cartilage matrix synthesis. This research
has identified substances, termed chondroprotective agents, which counter
the arthritic degenerative processes and encourage normalisation of
the synovial fluid and cartilage matrix. Chondroprotective agents are
compounds that stimulate chondrocyte synthesis of collagen and proteoglycans,
as well as synoviocyte production of hyaluronan, inhibit cartilage degradation
and prevent fibrin formation in the subchondral and synovial vasculature.
Examples of compounds that exhibit some of these characteristics are
the endogenous molecules of articular cartilage, including Hyaluronic
Acid, Glucosamine and Chondroitin Sulphate.
Related Articles:
Glucosamine and Chondroitin Sulphate (Matrix Enhancement Therapy)
Numerous studies have demonstrated that glucosamine stimulates the
synthesis of proteoglycans and collagen by chondrocytes. Since osteoarthritis
(OA) results when cartilage breakdown exceeds the chondrocytes' synthetic
capacity, providing exogenous glucosamine increases matrix production
and seems likely to alter the natural history of OA. Glucosamine also
has a mild antiinflammatory activity that is unrelated to prostaglandin
metabolism. In randomised, double-blinded, placebo-controlled clinical
trials using oral preparations, glucosamine salts have been verified
as efficacious in the management of OA, and have not demonstrated any
toxicity, severe side-effects, or abnormal clinical, biochemical, or
haematological changes. Chondroitin sulphate is the most abundant glycosaminoglycan
in articular cartilage. It plays an important structural role in articular
cartilage, notable for its role in binding with collagen fibrils. As
a chondroprotective agent, it has a metabolic effect as well: its action
is to competitively inhibit many of the degradative enzymes that break
down the cartilage matrix and synovial fluid in OA. Because of the additional
mechanism of action is via the prevention of fibrin thrombi in synovial
or subchondral microvasculature, chondroitin sulphate has been investigated
for its anti-atherosclerotic effect. When used together, it seems that
glucosamine and chondroitin sulphate combine effects to stimulate the
metabolism of chondrocytes and synoviocytes, inhibit degradative enzymes,
and reduce fibrin thrombi in peri-articular microvasculature. Numerous
clinical studies performed on horses at US veterinary schools have supported
this combination and synergistic effect.
There is a growing body of evidence for the efficacy of glucosamine
in symptom modification, and, given the low level of adverse side effects
noted from these products and the relatively low cost, it may be reasonable
for some patients with knee osteoarthritis to try taking glucosamine.
It should be noted, however, that a very recent review co-authored by
a senior and highly respected academic rheumatologist in the UK concluded
"there is more confusion and hype than magic about glucosamine".
The authors cautioned against its wholesale use and recommended the
need for "further large clinical trials without company interference".
Human randomised, double-blind clinical trials are currently underway.
Further
Information:
- The Rationality of Nutraceuticals. Cosamin DS, Nutramax Laboratories.
- Glucosamine and Chondroitin Sulphate Clinical Trials. AAOS Orthopaedic Connection, October 2000.
- Glucosamine and Chondroitin Sulphate. AAOS Orthopaedic Connection, June 2001.
- N Bellamy, SG Lybrand. Glucosamine therapy: does it work? eMJA 2001.
- T E McAlindon, M P LaValley, J P Gulin, D TFelson: Glucosamine and Chondroitin for Treatment of Osteoarthritis:
A Systematic Quality Assessment and Meta-analysis. JAMA March 15, 2000.
- Jiri Chard and Paul Dieppe. Glucosamine for osteoarthritis: magic, hype, or confusion? It's probably safe - but there's no good evidence that it works.
Editorial, BMJ 2001;322:1439-1440 ( 16 June )
Viscosupplements
With increased understanding of the pathogenesis of osteoarthritis
new therapies are being developed, one of which is viscosupplementation
with hyaluronic acid. Viscosupplementation is the term for a therapy
that aims to be chondroprotective by restoring the fluid properties
of the tissue matrix in osteoarthritis sufferers by means of intra-articular
injections if highly purified viscoelastic solutions of sodium hyaluronate
(HA, also known as hyaluronan). The use of viscosupplementation is based
on the observation that there is a decrease in viscosity and elasticity
of the synovial fluid in osteoarthritis and that the native hyaluronic
acid in osteoarthritic knees has a lower molecular weight than of that
found in normal healthy knees. Replenishing the hyaluronic acid component
of normal synovial fluid may play a role in supplementing the elastic
and viscous properties of synovial fluid, which may help relieve the
signs and symptoms related to osteoarthritis and improve function. Intraarticular
injections of hyaluronic acid (HA) are widely used in the Asian and
European orthopaedic communities for controlling the pain and loss of
joint function resulting from osteoarthritis. In more than 10 years,
it has been used in approximately one million patients in 20 countries,
with an excellent safety record. Treatment comprises of three weekly
intraarticular injections. HA is well tolerated with no demonstrable
toxicity and only a few side effects (transient injection site pain
and swelling). The new generation of bio-fermented hyaluronic acid is
exceptionally pure and contains no animal protein and no residual cross
linking reagents. This is the purest and closest product to the naturally
occurring substance.
The injectable substance is hyaluronate, a naturally occurring viscoelastic
agent that supposedly acts as a shock absorber and lubricant in the
knee joint. Preliminary results of animal studies demonstrate that intraarticular
injection of hyaluronic acid may have protective effects on articular
cartilage. Because it is injected directly into the joint, the onset
of action is fairly rapid. Possible mechanisms by which HA may act therapeutically
include: providing additional lubrication of the synovial membrane,
and controlling permeability of the synovial membrane, thereby controlling
effusions. Other possible, though less certain, mechanisms include:
promotion of cartilage matrix synthesis and reaggregation of preoteoglycans.
However, the exact mechanisms of action, articular cartilage changes
and short and long term results remain unknown.
In recent years, the concept of viscosupplementation has gained widespread
acceptance in the USA and Europe, and to a limited extent in the UK,
as a new treatment for the pain management in OA of the knee. There
is no doubt that viscosupplementation represents valuable addition to
current treatments for osteoarthritis and an alternative treatment,
especially when other forms of treatment have failed.
Further
Information:
Weight Management
Because your weight can have an effect on your knee pain, the body
mass index calculator can help you where you are in terms of appropriate
weight for your height. The body mass index (BMI) has been the medical
standard for obesity measurement since the early 1980s.
Over the years, slimming has become big business. There have been
many slimming crazes which may have left you confused about the best
way to loose weight. Unfortunately there is no miracle cure. ' Crash'
diets are usually unbalanced and designed to be used for only a few
weeks. Although some can be effective in the short run, most people
find that they put weight back on as soon as they return to normal eating.
The only way to lose weight permanently is to change your eating
habits. Realistically you can expect to lose about 1lb (1/2kg)
per week, which is safe and sensible rate of weight loss. Do at least
30 minutes of exercise, like brisk walking, most days of the week. The
idea is to use up more calories than you eat. You need to use up the
day's calories and some of the calories stored in your body fat.
This page was updated on: 3 June 2009
Site last updated on: 11 Feb 2011
 Disclaimer: This website is a source of information
and education resource for health professionals and individuals
with knee problems. Neither Chester Knee Clinic nor Vladimir Bobic
make any warranties or guarantees that the information contained
herein is accurate or complete, and are not responsible for
any errors or omissions therein, or for the results obtained from
the use of such information. Users of this information are encouraged
to confirm the accuracy and applicability thereof with other sources.
Not all knee conditions and treatment modalities are described
on this website. The opinions and methods of diagnosis and treatment
change inevitably and rapidly as new information becomes available,
and therefore the information in this website does not necessarily
represent the most current thoughts or methods. The content of
this website is provided for information only and is not intended
to be used for diagnosis or treatment or as a substitute for consultation
with your own doctor or a specialist. Email
addresses supplied are provided for basic enquiries and should
not be used for urgent or emergency requests, treatment of any
knee injuries or conditions or to transmit confidential or medical
information. If you have sustained a knee injury or have a medical condition,
you should promptly seek appropriate medical advice from your local
doctor. Any opinions or information,
unless otherwise stated, are those of Vladimir Bobic, and in no
way claim to represent the views of any other medical professionals
or institutions, including Nuffield Health and Spire Hospitals. Chester
Knee Clinic will not be liable for any direct, indirect,
consequential, special, exemplary, or other damages, loss or injury
to persons which may occur by the user's reliance on any statements,
information or advice contained in this website. Chester Knee Clinic is
not responsible for the content of external websites.
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