Osteoarthritis

William S. Wilke

PREVALENCE AND INCIDENCE

Osteoarthritis is the most prevalent form of arthritis in the United
States, affecting more than 70% of adults between 55 and 78 years of
age.5 Women are affected more than men.5,6 Hip osteoarthritis is
more common in Western populations, suggesting that race and
environmental factors might also be important.5 The incidence of
symptomatic knee osteoarthritis is 1% per year, with a radiographic
incidence of 2% per year. The rate of radiographic progression has
been estimated at about 4% per year.6

PATHOPHYSIOLOGY
Understanding the metabolic pathways at the molecular level has
greatly enhanced our understanding of the tissue factors involved.7
Although the role of inflammation in osteoarthritis has been
unclear for a long time, significant progress has been made in more
recent years. The molecular pathways involved are being more clearly
defined, and this is an area of intense ongoing research. Studies also
show that there are ongoing inflammation and synovitis that result
in permanent joint damage.1,5,8 At times, this may be more striking,
with flares of symptoms or joint effusions. Effusions can be very large
at times, and we have aspirated more than 100mL of fluid from an
acutely swollen knee on more than one occasion. Biopsies of
synovium from patients with osteoarthritis show more inflammatory
infiltrates than normal controls do.
Some patients appear to have a more hereditary form of this
disease. The striking features are usually seen in women who, shortly
after menopause, develop distal (Heberdens nodes) and proximal

SYMPTOMS, SIGNS, AND DIAGNOSIS

Stiffness, joint pain, and swelling are the earliest symptoms of osteoarthritis. In contrast to inflammatory arthritis, the pain of osteoarthritis is often exacerbated by activity or weight bearing and relieved
by rest. Early symptoms are usually of an insidious nature and often
do not correlate well with radiographic abnormalities. Later, extensive bone changes, muscle weakness, and loss of joint integrity can
lead to more-dramatic joint deformity and disability. Physical findings include painful limitation of movement, bony crepitus, and,
occasionally, joint effusions and joint line or bone tenderness. As the
disease progresses, more permanent joint deformities can occur in
the forms of contractures, osteophytes, and loss of joint function.
Synovial fluid analyses and laboratory investigations are generally
not diagnostic. Their utility lies mainly in excluding other causes for
the patients symptoms or other common forms of arthritis such as
crystal deposition diseases. Newer studies using markers of bone,
cartilage, and synovium turnover might help identify patients who
have a more rapidly progressive form of joint disease, but they are
not recommended in routine clinical practice. Data on high-sensitivity C-reactive protein have been reported, with somewhat conflicting findings. Elevated levels of C-reactive protein appear to correlate
best with symptoms of pain and stiffness rather than extent or progression of disease.11
Radiographic studies are reserved for patients with symptoms.
They are useful in excluding other causes of the patients symptoms
and in evaluating the extent of joint pathology. However, although
radiographs might show osteoid changes such as joint-space narrowing, effusions, bone cysts, and osteophytes, radiographs are limited
in sensitivity and in their ability to show nonosseous structures.
Ultrasound, computed tomography, and magnetic resonance
imaging (MRI) might show more extensive joint detail. Although
changes in soft tissue and cartilage are better visualized by MRI than
by radiographs, and MRI is more sensitive for picking up early bone
changes, this is generally unhelpful to the practicing physician.
Felson and colleagues have shown that men with osteoarthritis of the

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R H E U M AT O L O G Y A N D I M M U N O L O G Y

Osteoarthritis (also known as degenerative arthritis, hypertrophic

arthritis, or age-related arthritis) implies an inflamed joint by its very
name, but for a long time the role of inflammation in osteoarthritis
has been somewhat controversial. The pathology reflects the result
of joint disease, with loss and erosion of articular cartilage, subchondral sclerosis, and bone overgrowth (osteophytes).
Rather than one uniform disease, osteoarthritis may be a primary
or an idiopathic phenomenon, or it may be secondary to some other
disorder. Osteoarthritis is also commonly seen as a secondary form
of arthritis in patients with other inflammatory arthritides, such as
rheumatoid arthritis. Mechanical and genetic factors play roles in the
development of this disease as well. Histologic evidence clearly shows
ongoing inflammation and cartilage destruction in osteoarthritis,
although not to the same degree as in other arthritides, such as rheumatoid arthritis.1,4,5

(Bouchards nodes) interphalangeal joint involvement in their hands,

which eventually leads to the characteristic bony swelling and correlates with the presence of radiographic knee involvement.8 Previous trauma or other prior joint insults, such as inflammation,
infection, or avascular necrosis, increase the risk of developing osteoarthritis at that anatomic site.1,8
Histologically, articular cartilage comprises chondrocytes and
their extracellular matrices. Three distinct zones are recognizable:
superficial, middle, and deep. Mechanical or inflammatory injury
that disrupts these zones can lead to irreparable damage and to
further inflammation and cartilage degradation as the body attempts
to heal itself. In essence, there is a defective repair mechanism, resulting in scarring, thinning, and erosion of the articular cartilage in the
joints of subjects with osteoarthritis.9 Several cytokines, such as
interleukin-1 and transforming growth factor , proteases (the
most important of which is matrix metalloprotease), and nitric oxide
synthetase all appear to be essential for cartilage degradation in the
pathogenesis of osteoarthritis. It was previously believed that bone
changes occur later in this disease, but newer evidence suggests that
subchondral bone changes might take place earlier than previously
suspected.10 Increased production of bone and cartilage degradation
products has been shown to herald more rapid disease progression.4

DEFINITION

John Carey
S E C T I O N 13

Osteoarthritis, which is the most common form of arthritis in the

United States and other Western countries, is increasing in incidence
as the population ages, and it is likely to rise further with the obesity
epidemic. Significant disability and loss of function are associated
with this disease, and its management is an enormous cost to the
health care system. Progress in prevention and treatment has been
slow, related in part to the insidious onset and generally slow progression of the disease.1-3 As a result, clinical trials can take many
years to show a significant disease benefit. Therefore, despite its being
the most prevalent form of arthritis, few long-term clinical trials have
studied the therapeutic outcomes.

and

S E C T I O N 13

R H E U M AT O L O G Y A N D I M M U N O L O G Y

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Osteoarthritis

knee who have MRI evidence of subchondral bone bruising or

marrow edema experience a more rapid progression of their disease
than men who do not have these signs. Joint malalignment correlates
strongly with the presence of the bone marrow lesions.10 In addition,
asymptomatic patients with osteoarthritis might have significant
abnormalities on MR imaging, making abnormal findings even
harder to interpret.12 These more-expensive imaging modalities are
usually reserved for evaluating other possible causes of symptoms,
such as meniscal tears and tumors. Until it can be shown that a
therapeutic intervention can significantly prevent or retard the progression of this disease, the role of these imaging modalities in osteoarthritis is of limited value.

Nonacetylated Salicylates

TREATMENT

Systemic steroids are not indicated in the management of osteoarthritis. However, local intra-articular injection of corticosteroids can
provide significant relief of pain and stiffness, and despite the evidence in randomized trials, clearly some patients have very longlasting pain relief from a single injection. This should be performed
in a sterile manner by physicians experienced with this technique;
side effects such as infection, bruising, lipodystrophy, and osteonecrosis are rare with careful technique. Most of the benefit in randomized, double-blind, placebo-controlled trials seems to have occurred
soon after the injection, and improvement of symptoms may be
greatest in those with joint effusion.14,15 Intra-articular triamcinolone
40mg injections every 3 months for 1 to 2 years showed no effect on
radiographic progression.15
Synovial fluid should be aspirated, if possible, with an aseptic
technique before injection. The fluid should be sent for the usual
studies such as Gram stain, culture, cell count, and differential, and
an extensive examination for crystals should be performed by a
person familiar with this technique. Other studies may be performed
as the situation dictates. Studies such as fluid pH, viscosity, glucose,
antinuclear antibody, and rheumatoid factor are unhelpful in most
circumstances.

Treatments have not been shown to reverse this disease, although

some treatments can halt its progression. The goal of treatment is
adequate pain relief and preservation of function. The American
College of Rheumatology2 (ACR) and the European League Against
Rheumatism (EULAR) have published guidelines for managing hip
and knee osteoarthritis.
Weight loss, even small amounts, can significantly benefit overweight arthritis patients. Relaxation programs and moderate exercise, good nutrition, and education can all help relieve suffering in
arthritis patients. Caring health care professionals can alleviate worry
and help a patient to achieve realistic goals. Devices such as canes,
supports, and braces can take some stress off the affected joint.
Avoiding aggravating factors such as trauma, excessive weight gain,
or overly strenuous exercise is essential. Other analgesic therapies,
such as heating pads or ice packs, also alleviate suffering. Care should
be taken, as in all pain-related illnesses, to treat concomitant aggravating factors, such as psychosocial stress or other painful maladies,
such as secondary bursitis.2,3,5

Analgesics and Anti-Inflammatories

Acetaminophen (paracetamol in Europe) is generally recommended
as first-line pharmacologic therapy. Acetaminophen is a relatively
safe treatment and has significantly lower gastrointestinal (GI), renal,
and cardiovascular toxicities than other medications. When taken
on a regular basis, doses of 500 to 750mg three to four times daily
can provide substantial relief. Care should be taken not to exceed
4g/day.2,3
Nonsteroidal anti-inflammatory drugs (NSAIDs) can provide
significant acute relief in patients with osteoarthritis. However,
because osteoarthritis occurs more commonly in older patients who
often have other comorbidities, the use of NSAIDs is limited by their
potential for or actual side effects. Notably, they can cause or worsen
GI hemorrhage, renal insufficiency, congestive heart failure, and
hypertension.
Several agents (e.g., rofecoxib, celecoxib) that specifically inhibit
cyclooxygenase-2 (COX-2) are approved in the United States (by the
U.S. Food and Drug Administration [FDA]) and in Europe for use
in arthritis patients. Although they are more expensive than overthe-counter generic drugs, they have a better GI safety profile. The
concern with these newer agents, as for the older NSAIDs, is that
there may be an increased risk of cardiovascular events for patients
taking these medications.13 Indeed, one of these agents (rofecoxib
[Vioxx]) was withdrawn from the market because of evidence documenting such side effects. Whether these findings are specific to
rofecoxib or represent a class effect remains to be determined. They
should be used with extreme caution or not at all in patients with
renal or cardiovascular disease.
Topical aspirin or NSAID preparations, which are more widely
available in Europe, are an alternative to oral medications. However,
the incidence of side effects from NSAIDs is often dose related, and
thus they should probably be reserved for acute flares or more recalcitrant disease.

Nonacetylated salicylate compounds such as choline magnesium trisalicylate (Trilisate) 500 to 750mg two or three times daily are effective therapies for many patients, and we have had success using this
group of drugs. These medications have fewer adverse GI effects than
regular aspirin compounds or NSAIDs and provide a less-expensive
alternative to the COX-2 inhibitors. Salicylate levels can also be measured relatively easily in serum, similar to other pharmaceutical compounds, although this is not routine practice.

Steroids

Alternative Treatments
Viscosupplements, although approved by the FDA, appear to provide
little more relief than sham injections. Despite the promise for these
drugs, well-performed placebo-controlled trials have had disappointing results.16,17 Thus, we do not recommend routine use of
intra-articular hyaluronate or its derivatives until there is stronger
evidence that they are clearly beneficial.
Many patients with osteoarthritis use alternative therapies in an
attempt to relieve their suffering. Natraceuticals have shown some
promise in this regard. Glucosamine and chondroitin sulfate are by
far the most-studied agents in this category and have been shown in
several studies to be as effective as acetaminophen and NSAIDs, with
significantly fewer adverse effects. These agents appear to significantly alleviate pain and suffering by an unknown mechanism. They
have a slow onset of action (placebo-controlled trials show that it
takes several weeks to see an effect in the treated groups), and they
appear to have a more sustained post-treatment effect than NSAIDs
or analgesics.1,3,18,19 A 3-year placebo-controlled trial showed that
glucosamine might retard radiographic progression.19 We recommend trying glucosamine and chondroitin sulfate at a dose of 1200
to 1500mg daily in most patients with osteoarthritis, given that the
safety profile and efficacy are similar to those of NSAIDs and acetaminophen.
Acupuncture, although used by many patients, appears to be no
better than sham needling in controlled trials,5 and it is not without
its own risks, which include reports of hepatitis transmission and
pneumothoraces.

Narcotic Analgesics
Narcotic analgesics should be reserved for patients with severe joint
disease and intolerable suffering who are not candidates for other

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Osteoarthritis

Antidepressants

Suggested Readings

The efficacy of arthroscopy for osteoarthritis remains controversial. It is under review by the ACR and is not recommended in the
2003 EULAR guidelines.2,3 Progress in joint replacement surgery has
been remarkable in the past few decades, particularly for knee
and hip arthritis. Arthroplasty is now used to treat many patients
with severe osteoarthritis, especially those who are appropriate surgical candidates and for whom more-conservative measures have
failed.
Joint replacements can wear out after an average of 10 to 15 years,
although some patients do well for much longer. Newer components
and improved techniques might increase the longevity of these
replacements in the future. Reoperation after the original replacement surgery may be more complex and can have higher failure and
infection rates.

CONCLUSIONS
Osteoarthritis is the most common form of arthritis in the United
States. The incidence increases with advancing age. Many patients
can achieve significant relief of their symptoms with appropriate
care. Current therapies are being investigated to see if they improve
the long-term outcomes of this disease. Ongoing research is aiming
to identify patients who have a more rapidly progressive illness, and
it is evaluating disease-specific molecular pathways as potential new
targets for intervention. Advances in joint replacement surgery have
made this an excellent treatment for many patients with more-severe
disease.

Altman RD, Hochberg MC, Moskowitcz RW, Schnitzer TJ: Recommendations for the
medical management of osteoarthritis of the hip and knee: 2000 update. American
College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis
Rheum 2000;43:1905-1915.
Brooks P: Inflammation as an important feature of osteoarthritis. Bull World Health
Organ 2003;81:689-690.
Felson DT, Anderson JJ: Hyaluronate sodium injections for osteoarthritis: Hope, hype,
and hard truths. Arch Intern Med 2002;162:245-247.
Gaffney K, Ledingham J, Perry JD: Intra-articular triamcinolone hexacetonide in knee
osteoarthritis: Factors influencing the clinical response. Ann Rheum Dis 1995;54:379381.
Jordan KM, Arden NK, Doherty M, 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.
Lin EHB, Katon W, Von Korff M, et al: Effect of improving depression care on pain and
functional outcomes among older adults with arthritis: A randomized, controlled
trial. JAMA 2003;290:2428-2434.
Mainil-Varlet P, Aigner T, Brittberg M, et al: Histological assessment of cartilage repair:
A report by the Histology Endpoint Committee of the International Cartilage Repair
Society (ICRS). J Bone J Surg Am 2003;85A(suppl 2):45-57.
Mandell BF: COX-2 inhibitors: Balancing the hope, the hype, and the concern. Cleve
Clin J Med 2001;68:899.
Richy F, Bruyere O, Ethgen O, et al: Structural and symptomatic efficacy of glucosamine
and chondroitin in knee osteoarthritis: A comprehensive meta-analysis. Arch Intern
Med 2003;163:1514-1522.
Sturmer T, Brenner H, Koenig W, Gunther KP: Severity and extent of osteoarthritis and
low grade systemic inflammation as assessed by high sensitivity C reactive protein.
Ann Rheum Dis 2004;63:200-205.

References
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R H E U M AT O L O G Y A N D I M M U N O L O G Y

Surgery

Whether it is primary or secondary, osteoarthritis is

characterized by loss and erosion of cartilage, subchondral
sclerosis, and overgrowth of bone.
l The pathogenesis of osteoarthritis is driven by heredity,
prior insults to the joint, and mild-to-moderate local
inflammation.
l The diagnosis of osteoarthritis is made on the basis of
signs and symptoms of joint swelling, pain, and
hypertrophy in characteristic joints and is confirmed by
x-ray.
l Primary treatment of osteoarthritis includes joint
protection, strengthening the muscles around the joint,
weight loss for hip and knee osteoarthritis, and
acetaminophen.
l Nonsteroidal anti-inflammatory drugs are safest when
used intermittently.
l

Depression and arthritis are common and often coexist. Treatment

of depressive symptoms in older adults with arthritis resulted in
significantly less pain and depression and overall improvement in
health and quality of life.20 Thus, care should be taken to evaluate
and treat patients for concomitant depression when managing their
arthritis.

Summary

S E C T I O N 13

therapeutic interventions or for whom other therapeutic interventions have failed. Short courses, however, can be used effectively.
Less-potent medications, such as the new combination tramadol/
acetaminophen, should be tried first, reserving narcotic medications
for those who still have severe pain. Usual precautions should be
taken when prescribing these, such as counseling patients about their
correct use and addictive potential.

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