Osteoarthritis

BERNARD R. RUBIN, DO

Arthritis is a common, disabling condition that affects an increasing percentage of

the population. This article includes discussion of new theories of risk factors and
treatment paradigms.
(Key words: osteoarthritis, pain, joint injury)

rthritis is one of the most common

chronic debilitating diseases in the
United States. Age is the most powerful
risk factor for the development of
osteoarthritis, which is the most common
form of arthritis affecting Americans.
Osteoarthritis affects more than 21 million people in the United States,1 and radiography-demonstrated changes of
osteoarthritis occur in a majority of individuals by age 65 years and are seen in
more than 80% of persons older than 75
years.2 Because the US population is growing older, the prevalence of osteoarthritis is
increasing as well. Only 4% of the population in the United States was older than
65 years in 1900, but by the year 2030,
22% of the US population will be older
than 65. Therefore, by the year 2020, more
than 50 million persons in the United States
will be affected by arthritis, which will
increase the direct and indirect dollars spent
on arthritis care by more than 25%. More
than one third of the US expenditure on
healthcare in the United States in 1996
was devoted to providing care for individuals older than 65 years.3 Healthcare
expenditures rise as individuals age. More
Dr Rubin is professor of medicine and chief,
Division of Rheumatology, Department of Internal Medicine, University of Texas Health Science
Center at Fort Worth/Texas College of Osteopathic Medicine.
Dr Rubin is a member of the Speakers
Bureau of Pfizer, Pharmacia Searle, and Merck.
Correspondence to Bernard R. Rubin, DO,
Department of Internal Medicine, University of
Texas Health Science Center/Texas College
of Osteopathic Medicine, 3500 Camp Bowie
Blvd, Ft Worth, TX 76107-2970.
E-mail: [email protected]

than 40% of persons older than 85 years

require assistance with their activities of
daily living and an increasing number of
services that are offered in long-term care
facilities. Osteoarthritis is the most common reason for total hip and total knee
replacement.

Risk factors
Age
Osteoarthritis causes symptoms in approximately 12% of US adults between the
ages of 25 and 74 years. The increased
incidence of osteoarthritis occurs most
among women older than 45 years.4 Before
the age of 50 years, the problems of
osteoarthritis in most joints is higher in
men than in women, but after the age of 50
years, women are more affected, usually
in their hands, feet, and knees, than men.
Osteoarthritis can be defined either by
symptoms, radiographic findings, or by
an underlying pathologic process.
Osteoarthritis of the hips and knees has
the greater clinical impact because these
joints are weight-bearing. Osteoarthritis is
multifactorial so that risk factors other
than simply advancing age may be important (Figure 1). There have been associations to obesity, quadriceps muscle weakness, joint overuse or injury, genetic
susceptibility, and developmental abnormalities, among others.

Ethnic characteristics
The evidence is conflicting regarding ethnic differences in osteoarthritis of the hip
and knee. Although one study has indicated higher rates of knee osteoarthritis in
African American women but not men,

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another study from the rural South suggested no differences in disease prevalence.5,6 Ethnic differences in the risk of
development of osteoarthritis could be
explained by differences in body mass
index, for example, so other factors may
also be important.

Estrogen replacement therapy and bone

mineral density
Estrogen replacement therapy (ERT) has
been associated with significant reduction
in moderate to severe symptomatic
osteoarthritis in the hip in white postmenopausal women. Although cohort
studies have reported that women taking
estrogen have a decreased prevalence in
incidence of radiographic findings of
osteoarthritis, case-controlled studies have
been inconsistent in their findings.7-9 It
may also be that women who are on ERT
are in general healthier than women who
are not on ERT, and therefore, there may
be some confounding because of these
healthy habits among women who are
hormone users.
There seems to be an inverse relationship between osteoarthritis and osteoporosis
in that a higher bone mineral density is
associated with an increased prevalence of
knee and hip osteoarthritis, whereas
women with low bone density and osteoporosis seem to have a decreased incidence
of osteoarthritis. The role of estrogen in
osteoarthritis is clearly complex.

Nutritional factors
Vitamins and arthritis have been linked for
many years. Vitamins A, C, and E are
major antioxidants in the diet. They all
have been associated in one way or the
other with osteoarthritis. Vitamin D may
also play a role in osteoarthritis. Nutritional factors play a role in osteoarthritis
by either protecting against oxidative damage in the joint, modulating the inflammatory response affecting cellular differentiation within the arthritic joint, or
altering biologic actions related to both
bone and collagen synthesis.10 In individuals who have a high intake of vitamin C,
there has been an associated decrease in
the risk for progressive osteoarthritis as
diagnosed on x-ray studies. These individuals have also had less knee pain than
individuals who take less vitamin C. Vitamin D may have some direct effect on
bone-remodeling cells. Once again, there
has been about a threefold increase in the
risk involvement of osteoarthritis in persons with low vitamin D intake. No evi-

Rubin Osteoarthritis

dence exists, however, that a low dietary

intake of vitamin D influences the risk
for development of osteoarthritis in someone who has previously had a nonarthritic knee. The low levels of dietary intake of
vitamin D are associated with progression of established osteoarthritis of the
knee. This role for vitamin D might be
attributable to its potential to contribute
to the immunologic response and inflammatory products. Vitamin D receptors
have been found within arthritic joints.11
Therefore, dietary levels of vitamin D may
be relevant to osteoarthritis.
Unfortunately, people rarely consume
each of these vitamins and other nutrients as independent agents. Dietary supplements often contain multiple vitamins
and minerals. Therefore, it is difficult to
isolate the effect of one vitamin or other
nutritional supplement in the etiology or
the progression of osteoarthritis.

Genetic susceptibility
A genetic susceptibility to osteoarthritis now
appears to be evident in some cases. Up until
about 20 years ago, osteoarthritis was thought
to simply be due to the degeneration of cartilage within joints. Therefore, medical therapy would have limited benefit because
osteoarthritis was simply a mechanical problem. Inflammation is present within
osteoarthritic joints.12 Genetic factors probably account for at least half of all cases of
osteoarthritis of the hands and hips. This
probability raises the possibility at some point
that gene therapy might be an approach to
therapy in the future.

Obesity
Obesity is clearly a risk factor for
osteoarthritis, especially osteoarthritis of
the knee. Felson and colleagues13 observed
that women who lost only an average of 11
pounds were able to decrease their risk of
development of osteoarthritis by up to 50%.
The relationship between obesity and
osteoarthritis of the hip is weaker. A joint
can be overloaded simply by the increase in
weight. For every step that a person takes,
a force of approximately three times ones
body weight is transmitted across the knee
joint. Therefore, it is easy to see why an
increased risk of osteoarthritis occurs in
overweight persons.
Obesity is a major problem in the United States, and despite efforts to improve
physical fitness in school-age children and
adults, the portion of the population considered obese has increased by more than
50% in the past decade.14

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Checklist

Age
Obesity
Joint injury
Muscle weakness
Ethnic characteristics
Nutritional factors
Genetics

Figure 1. Risk factors for osteoarthritis.

Muscle weakness
Muscle weakness also plays a role in the
development of osteoarthritis. It is not
known whether quadriceps muscle weakness precedes or follows osteoarthritis and
whether its cause is diffuse atrophy of the
muscles or whether there may be a sensory
function of muscle which becomes inhibited and leads to a change in motor function. The knee is the most common joint
discussed with regard to muscle dysfunction, primarily because the muscles around
the knee are so easily investigated. Muscle
has several functions including movement,
the maintenance of joint stability, shock
absorption, and proprioception. Weak
muscles fatigue more quickly, so any dysfunction in muscle would compromise
the protective effects and could lead to
joint instability, joint pain, and abnormal
biomechanical loading on the joint. Over
time, this increased stress leads to changes
in cartilage and bone consistent with
osteoarthritis. Studies have shown that
even a relatively small increase in quadriceps muscle strength can result in a significant decrease in the odds of having
osteoarthritis of the knee.15 Criticism of
rehabilitation is that even if it is effective,
as soon as the exercising stops, then the
benefits are lost. Improvement in knee
pain and function can certainly occur after
exercise programs end.

Joint injury
Congenital dislocation of the hip is associated with an increased incidence of
osteoarthritis. In addition, major joint
injuries are common causes of osteoarthritis. Jobs with repetitive motion may cause
muscle fatigue and therefore increase the
risk of osteoarthritis. Jobs that require
squatting associated with heavy lifting are
associated with high rates of osteoarthritis of the lower extremities. Jobs that
require squatting and turning at the same

time may cause up to 30% of knee

osteoarthritis in men.16
Athletic activities can also increase the
risk of major bone damage due to repetitive use. Jogging appears to be a minimal risk to the development of osteoarthritis.17 Other sport activities such as football
and soccer put their participants at more
risk for knee injuries. Overuse injuries
and twisting of joints may also lead to
degenerative arthritis such as that seen in
baseball pitchers elbows. Appropriate
training to improve joint stability and the
use of proper equipment, which would
either pad or brace a joint, could potentially decrease these sports-related injuries
to a certain degree.

Treatment of patients with

osteoarthritis
Because no known cure exists for
osteoarthritis, physicians who care for
patients with osteoarthritis face difficulties.
The increasing burden of disease and disability associated with osteoarthritis presents a significant public health problem.
Such treatment certainly needs to decrease
pain and improve function, while trying to
avoid side effects, if possible. Nonpharmacologic modes of therapy (Figure 2),
including exercises to improve muscle
weakness and strengthen joint laxity, are
important. New oral medications to
decrease pain and even nutriceuticals are
now widely prescribed. Last, surgery is
appropriate in selected individuals.

Nonpharmacologic therapy
Nonpharmacologic management of
osteoarthritis includes weight loss, education for patient and family, physical
and occupational therapy, aerobic conditioning exercises, and the use of appropriate assistive devices such as canes and
better footwear to decrease the mechanical stress on joints.
These nondrug treatment modalities
may limit the need for analgesic agents,
and therefore could potentially spare
patients the side effects of drugs. Physical
therapy in osteoarthritis includes range-ofmotion exercises, muscle-strengthening
exercises, and the use of assistive devices.
If a person is unable to move a joint
through an entire range of motion
because of pain, then the prior use of
heat will help to stretch tissues and therefore can make it easier to exercise.
Quadriceps-strengthening exercises are
very important. The Fitness Arthritis in
Seniors Trial (FAST)18 demonstrated that

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quadriceps muscle strengthening and aerobic exercise will decrease pain and disability. A recent study by Deyle and associates19 evaluated the effectiveness of
manual physical therapy for osteoarthritis of the knee conducted by physical
therapists who had formal training in
such treatment. They hypothesized that
physical therapy that consisted of manual therapy to the knee, hip, ankle, and
lumbar spine combined with traditional
range-of-motion muscle strengthening
and cardiovascular exercises would be
more effective than placebo for improving function, decreasing pain, and increasing functional capacity. Patients were
actually evaluated 1 year after completing
the study. Although the active portion
of the treatment lasted only 8 weeks,
there were more knee surgeries in the
patients received the placebo than in the
treatment group 1 year after the active
therapy ended. Therefore, the authors
concluded that the patients with
osteoarthritis of the knee who were treated with a combination of manual physical therapy and exercise had statistically
significant improvements in pain relief
and functional ability compared with a
placebo group. The effectiveness of this
treatment persisted 1 year after the conclusion of this study. The manual therapy consisted of passive physiologic and
accessory joint movements, muscle
stretching, and soft tissue mobilization
primarily applied to the knee. In addition, the treatment group received a standardized knee exercise program at each
session.

Pharmacologic treatment
Pharmacologic treatment modalities for
osteoarthritis consist of systemic drugs,
including analgesics, nonsteroidal antiinflammatory drugs (NSAIDs), opioid
analgesics, glucosamine, and chondroitin
sulfate (Figure 3). In addition, there is
intra-articular therapy consisting of corticosteroids and hyaluronic acid. Topical
therapy is also an option.
For many patients with osteoarthritis,
simple analgesics such as acetaminophen
offer pain relief comparable to that
achieved with an NSAID.20 In one study,
treatment with high doses of acetaminophen was compared to treatment
with low and high doses of ibuprofen for
4 weeks. With the exception of pain at
rest, no meaningful or significant differences were found between the three treatment groups. Although acetaminophen

Checklist

Weight loss
Physical therapy
Occupational therapy
Patient education
Aerobic conditioning exercises
Assistive devices/footwear

Figure 2. Nonpharmacologic treatment of

osteoarthritis.

Checklist

 Systemic treatment modalities

Nonopioid analgesics

Nonsteroidal anti-inflammatory
drugs

Opioid analgesics

Glucosamine and chondroitin
sulfate
 Inra-articular therapy

Corticosteroids

Hyaluronic acid
 Topical analgesics

Figure 3. Pharmacologic treatment of

osteoarthritis.
is safe, it has been associated with some
important side effects such as prolongation
of the prothrombin time. In large doses, it
may be associated with liver toxicity.
Tramadol hydrochloride (Ultram) is a
synthetic opioid agonist approved for the
treatment of moderate to severe pain. Tramadol may be comparable to ibuprofen in
the relief of pain of osteoarthritis of the hip
and knee.21 Side effects of tramadol
include nausea, constipation, drowsiness,
and seizures.
NSAIDs offer relief of pain and inflammation associated with osteoarthritis but
also have side effects. Currently, the choice
between a nonselective NSAID and a
cyclooxygenase-2 (COX-2) specific
inhibitor is an option that did not exist
before January 1999. Risk factors for
upper gastrointestinal bleeding in patients
treated with NSAIDs include a history of
peptic ulcers, the use of oral corticosteroids or anticoagulants, and age 65 years
or older. In addition, comorbid conditions

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and multiple-drug therapy may pose additional considerations for the use of COX2 specific inhibitors. Two COX-2-specific inhibitors, celecoxib (Celebrex) and
rofecoxib (Vioxx), have been approved
for use in patients with osteoarthritis.22,23
Two recently published long-term studies have shown differences between COX2 specific inhibitors and nonselective
NSAIDs with respect to major gastrointestinal clinical outcomes.24,25 Another
advantage of rofecoxib and celecoxib is
that neither drug has a clinically significant
effect on platelet aggregation or bleeding
time. At doses recommended for the treatment of osteoarthritis, these drugs appear
to be better tolerated than comparative
nonselective NSAIDs, and therefore, both
have become widely used in the treatment
of osteoarthritis. As with nonselective
NSAIDs, COX-2 specific inhibitors can
cause renal toxicity. In addition, celecoxib is contraindicated in patients with allergic reactions to a sulfonamide.
Alternatively, nonselective NSAIDs can
be combined with misoprostol (Arthrotec,
Cytotec) or omeprazole (Prilosec). In either
case, although there may be a decrease
in serious adverse upper gastrointestinal
events with these combinations of therapy, platelet aggregation would still be
inhibited.
Opioid analgesics can be used for severe
pain associated with osteoarthritis unresponsive to acetaminophen, tramadol, or
nonsteroidal anti-inflammatory drugs.
Glucosamine and chondroitin sulfate
have been used in the treatment of
osteoarthritis for more than 40 years. Products are found in both health food stores
and pharmacies. They have been purported
to decrease the pain of osteoarthritis. A
meta-analysis of 15 different studies was
recently published.26 Only controlled studies of at least 4 weeks duration were analyzed. Fifteen such studies were included,
and all but one was classified as positive.
The studies demonstrated moderate effects
for glucosamine and large effects for chondroitin. The authors concluded that the
quality of the studies was poor, and therefore, the methodologic problems could
have exaggerated the estimates of benefits. The National Institutes of Health is
currently supporting a multicenter, randomized, double-blind, placebo-controlled
study of patients taking glucosamine alone,
chondroitin sulfate alone, glucosamine
and chondroitin sulfate together, or placebo. Results are not expected for another 3
years.

Rubin Osteoarthritis

Complementary and alternative

treatment
In addition to the foregoing list of treatment modalities, use of topical analgesics
such as capsaicin cream may be useful to
decrease pain in osteoarthritis.
Complementary and alternative therapy is often used in the treatment of
osteoarthritis. A recent study of rheumatology patients27 showed that those with
osteoarthritis are the most frequent users
of alternative modes of treatment, including mind-body interventions, acupuncture, and manipulative therapy.
Behavioral interventions, specifically
telephone-based interventions, are intriguing. Obviously, telephones are found in
most households; therefore, studies have
shown that a telephone-based program
can be used to call patients to check on
their symptoms, review medication use,
and offer counseling.28

Surgical treatment
Last, surgical treatment of osteoarthritis
can be considered after failure of all other
nonsurgical modes of treatment. Arthroscopic surgery may alleviate symptoms
and is probably indicated before substantial joint space narrowing has
occurred. Total joint replacement represents a significant advancement in the
treatment of osteoarthritis. Total joint
replacement is among the most effective of
all modes of therapy, particularly for
osteoarthritis of the hip and knee.29
Younger patients may outlive the durability of the total joint replacement, and
therefore require revisions of their replaced
total joints. Recently, cartilage transplantation has become available. Only preliminary experimental and clinical studies
have been done to date.
The prospects for safer and more effective management are better than at any
time in the past. Not only are new drugs
being developed that will alleviate joint
pain in osteoarthritis, but surgical procedures are being developed as well. Nonpharmacologic and nonsurgical treatment
of osteoarthritis continues to be a mainstay
in the day-to day management of patients
with osteoarthritis.

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