|
- - - - - - - - - - - - - - - - - - - - - - - - -
General Joint Surgery Information
New Pain Medications
Review of Hyaluronic Acid, Glucosamine, Chondroitin Sulfate
Therapies for OA Pain
Osteoarthritis (OA) is the most common form of arthritis,
affecting up to 30 million Americans. Although joint replacement
has been a very successful treatment of advanced disease, no
reliable and effective treatment exists for the early stages
for osteoarthritis. Current approaches employed for this condition
include nonsteroidal anti-inflammatory medicines, exercise,
cortisone injections, arthroscopic surgery and osteotomy.
In the absence of reliable conservative treatments, alternative
therapies may be reasonably applied. Two such therapies that
are gaining popularity are hyaluronate injections and oral glucosamine/chondroitin
sulfate. To educate orthopedic surgeons about these therapies
for osteoarthritis, the following review has been developed
by the Academy's Committee on Biological Implants.
Injectable Therapies
The synovial fluid from osteoarthritic joints has a lower elasticity
and viscosity than the synovial fluid from normal joints. This
characteristic results in a decrease in the flow of synovial
fluid, which has led to the development of viscosupplementation
therapy. This therapy consists of injections of hyaluronate
into the knee joint in an attempt to improve the elasticity
and viscosity of the synovial fluid and thereby reduce pain.
The Food and Drug Administration (FDA) approved two hyaluronic
acid viscosupplementation products for the treatment of osteoarthritis
in 1997. Hyalgan®, manufactured by Fidia Pharmaceutical
Corp. and Synvisc®, manufactured by Biomatrix, Inc. Hyalgan®
is marketed to orthopedic surgeons by Orthologic and Synvisc®
is marketed by Wyeth-Ayerst.
Hyaluronate products are used in a series of three to five
weekly injections depending on the product. Average cost of
the entire series of injections is approximately $500. Studies
suggest the injections may have beneficial effects lasting 12
to 26 weeks.
The major implied benefit of hyaluronic acid (HA) therapy
is its replacement of OA Synovial fluid to resist in improved
mechanical action and improved lubrication of the joint. Other
stimulation of the body's own ability to reproduce hyaluronic
acid, as well as production of the proteins and sugars that
act as the "glue" that holds the cartilage cells together.
Additional proposed benefits have included inhibition of the
release of cartilage destroying enzymes and pain receptors in
joint tissue.
Adverse effects of the injectable products have been few and
mainly related to local inflammation at the site of injection
into the knee joint. Although several placebo-controlled clinical
trials performed in Europe have demonstrated a beneficial effect
of hyaluronate therapy, with effects persisting for a number
of weeks following the injections, one large randomized double-blind
placebo-controlled trial conducted in the United States failed
to demonstrate significant beneficial effects. Finally, the
existence of long-term cartilage protective effects, including
alteration of the natural history of osteoarthritis, by these
injectable compounds has not yet been shown.
Oral Therapies
The two compounds, glucosamine and chondroitin sulfate, taken
either singly or in combination, have been promoted as substances
that will improve the formation of proteoglycans, loss of which
is one of the earliest biochemical changes in osteoarthritis.
Proteoglycans are large water-binding molecules consisting of
proteins and sugars that act as major building blocks of cartilage.
Chondroitin sulfate is a long chain of repeating sugars that
act like "liquid magnets" to attract fluid into the
proteoglycan molecules. The fluid acts as a shock absorber,
as well as nourishes and lubricates the cartilage. The basis
for oral glucosamine and chondroitin sulfate as cartilage protective
therapies for cartilage degeneration is that they might shift
the chemical equilibrium in articular cartilage to favor synthesis
of proteoglycans and improved lubrication and nutrition of the
cartilage.
Several human trials have been conducted in Europe and Asia
which have been demonstrated the efficacy of these compounds
as judged by improvement in subjective symptoms of osteoarthritis
and improved range of motion. Benefits have been moderate with
approximately 50 percent to 80 percent of the treatment group
of patients showing improvement as opposed to 20 to 30 percent
in placebo groups.
One compound that recently has been touted to be more effective
than glucosamine and chondroitin sulfate taken singly is known
as Cosamin DS®. This compound includes a patented combination
of glucosamine, chondroitin sulfate, and manganese ascorbate.
Manganese and ascorbate have been added as cofactors for the
biosynthesis of proteoglycans. Whether or not this particular
combination is effective is yet to be determined in controlled
trials.
One of the reasons for the popularity of these new oral therapies
is the publication of The Arthritis Cure, authored by
Theodosakis et al, and published by St. Martin's Press in paperback
in 1997. This book reviews the use of chondroitin sulfate and
glucosamine in osteoarthritis. The book also reviews the use
if NSAIDs and makes recommendations for healthful diets, maintenance
of an ideal body weight, regular exercise and other reasonable
approaches to the treatment of osteoarthritis. There is no doubt
that some of the attention that is currently being paid to the
use of these oral therapies is a result of the advice given
in this book. Glucosamine and chondroitin sulfate are available
without prescription. A one-month supply costs between $15 and
$50.
New therapies that are being used for the treatment of osteoarthritis
include intra-articular injections of hyaluronic acid and oral
intake of glucosamine and chondroitin sulfate. FDA approval
was sought and achieved by the manufacturers of the injectable
therapies obviously require intra-articular injections; oral
therapies do not require prescriptions, but can be obtained
over-the-counter and are frequently sold through Internet outlets.
The role of these therapies appears to be additional or supplemental
to traditional therapies such as the use of NSAIDs or mild analgesics.
The literature on the injectable therapies as well as the oral
therapies suggests that these treatments will ameliorate the
pain of osteoarthritis over the short-term.
These therapies may delay the need for operative intervention
for pain relief, but there is no evidence to suggest that they
are cartilage protective in inhibiting the breakdown or increasing
the synthesis of cartilage in osteoarthritis. They seem to have
few adverse effects, and therefore, appear to be reasonably
safe. Nonetheless, further studies should be performed to document
clear efficacy. Until that time, widespread application is not
warranted. As with any new compounds, physicians recommending
these products should review package inserts to become familiar
with their use and adverse effects.
William W. Tomford is chairman of the Academy's Committee
on Biological Implants
|
