Seminar

Pathogenesis and management of pain in osteoarthritis

Paul A Dieppe, L Stefan Lohmander Lancet 2005; 365: 965–73
MRC Health Services Research
Summary Collaboration, Department of
Social Medicine, University of
The term osteoarthritis describes a common, age-related, heterogeneous group of disorders characterised
Bristol, Canynge Hall,
pathologically by focal areas of loss of articular cartilage in synovial joints, associated with varying degrees of Whiteladies Road, Bristol
osteophyte formation, subchondral bone change, and synovitis. Joint damage is caused by a mixture of systemic BS8 2PR, UK (P A Dieppe FRCP);
factors that predispose to the disease, and local mechanical factors that dictate its distribution and severity. Various and Institute of
Musculoskeletal Diseases,
genetic abnormalities have been described, but most sporadic osteoarthritis probably depends on minor
Department of Orthopaedics,
contributions from several genetic loci. Osteoarthritic joint damage may be associated with clinical problems, but the Lund University, Lund, Sweden
severity of joint disease is only weakly related to that of the clinical problem. For this reason the associations and (Prof L Stefan Lohmander MD)
pathogenesis of pain are in as much need of investigation as joint damage. Subchondral bone and synovium may be Correspondence to:
responsible for nociceptive stimuli, and peripheral neuronal sensitisation is an important feature, and can result in Dr Paul A Dieppe
p.Dieppe@bristol.ac.uk
normal activities (such as walking) causing pain. Central pain sensitisation can also occur, and psychosocial factors
are important determinants of pain severity. We present a stepwise approach to the management of osteoarthritis.

Introduction factors, concentrating on progression of joint damage

Osteoarthritis is a common disorder of synovial joints. It and persistence of pain. We then consider the genetics
is characterised pathologically by focal areas of damage of osteoarthritis, and the inter-related issue of the
to the articular cartilage, centred on load-bearing areas, phenotypic expression of the disease. Finally, we present
associated with new bone formation at the joint margins some principles of diagnosis, assessment, and
(osteophytosis), changes in the subchondral bone, management.
variable degrees of mild synovitis, and thickening of the
joint capsule (figure 1).1 When this disease is advanced it Joint damage and joint pain
is visible on plain radiographs, which show narrowing Radiography has been the main method used to define
of joint space (due to cartilage loss), osteophytes, and osteoarthritis for epidemiological purposes. Community-
sometimes changes in the subchondral bone (figure 2).2 based radiography studies show that this condition is
Osteoarthritis can arise in any synovial joint in the body, extremely common in older people.3,6,7 But frequency
but is most common in the hands, knees, hips, and data vary, partly because of population differences,
spine. A single joint could be involved, but more perhaps also because of the use of different cut-off
commonly several joints are affected. This condition is
strongly age-related, being less common before 40 years,
but rising in frequency with age, such that most people
older than 70 years have radiological evidence of
osteoarthritis in some joints.3
The clinical problems associated with these
pathological and radiographic changes include joint
pain related to use, short-lasting inactivity stiffness of
joints, pain on movement with a restricted range, and
cracking of joints (crepitus). Pain is particularly
important, and osteoarthritis is thought to be the biggest
cause of the high rate of regional joint pain in older
people.4,5 However, the correlation between radiographic
evidence of osteoarthritis and the symptomatic disease
is rather weak. This raises issues relating to the
definition of the so-called disease and to the extent to
which we should be studying the cause of joint damage,
or the causes of pain and physical disability in older Figure 1: Slab radiograph of (A) normal and (B) osteoarthritic femoral head
people. Radiograph of osteoarthritic joint shows marginal osteophytes, change in shape of bone, subchondral bone cysts,
and focal area of extensive loss of articular cartilage.

Scope
The purpose of this Seminar is to focus on three topical, Search strategy and selection criteria
important, inter-related, and controversial aspects of the
disorder. First, we consider the relations between joint We searched MEDLINE and Embase, combining the term “osteoarthritis” with “pain”,
damage and joint pain, before reviewing some data “genetics”, “genes”, “management”, or “treatment”.
about the risk factors and pathogenesis for each of these

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 Seminar
Figure 2: Anteroposterior radiograph of knee joint with osteoarthritis
Note the varus malalignment (resulting in "bow-legs") due to loss of cartilage
and therefore joint space width in medial compartment, and osteophyte
formation.
points to define the presence or absence of osteo-
arthritis, and because problems exist with the sensitivity
of the radiograph.8,9 The use of MRI and arthroscopy
make it clear that early osteoarthritic changes are not
apparent on the radiograph,10,11 but these techniques
cannot easily be used in population studies.
Joint pain is very common in older people in all
communities.12 Widespread chronic pain is present in
some 10–15% of the UK population at any one time.13
Regional joint pain is even more common, some 25% of
the population reporting knee pain or back pain in cross-
sectional studies.5 However, there are no valid criteria
for epidemiological use that allow us to say which people
with regional joint pain have osteoarthritis. The only
clinical criteria for this condition are those produced
some years ago by the American College of
Rheumatology,14 but they were derived from data that
compared hospital patients with a diagnosis of
osteoarthritis with those who had inflammatory joint
disease; these criteria are therefore of limited value and
are unlikely to be applicable to community-based
epidemiological studies.15 But nowadays the disease-
based, reductionist model of health is pre-eminent, so it
is not surprising that the high frequency of pain in joint
966
Osteoarthritic Both Radiographic
symptoms osteoarthritic
changes
Population
High risk
groups
Figure 3: Schematic relations between different groups in the community
Some people have risk factors for osteoarthritis, but no disease; some have
radiographic changes but no symptoms; and some have symptoms and signs
associated with osteoarthritis, and hence so-called classical osteoarthritis. Our
understanding of drivers of conversion from one of these states to another is
incomplete.
sites that are commonly affected by osteoarthritis has led
to the assumption that this disorder is the sole cause of
such pain. Is this assumption justified?
In the 1960s, John Lawrence and colleagues6 showed
that people with radiographic evidence of osteoarthritis
were more likely to have joint pain than were those
without any such changes, but also that severe
radiographic changes could be present with few or no
symptoms. More recent studies have confirmed and
extended these findings.3,16–20 It is clear that radiographic
evidence of joint damage predisposes to joint pain, but
that the severity of the joint damage on the radiograph
bears little relation to the severity of the pain
experienced.
Joint damage and joint pain are both common: many
people are susceptible to one or both (through either the
genetic or environmental risk factors outlined below).
But there are few data about the incidence (rather than
prevalence) of either event, and it is unclear what causes
the conversion from non-disease to disease (figure 3).
Risk factors associated with joint damage and
its progression
Problems with the definition of osteoarthritis, and the
populations used to study it, affect the data available
about risk factors. Many data about the risk factors for
joint damage are available from community studies that
have generally used the Kellgren and Lawrence X-ray
grading system to define osteoarthritis.8 In addition to
age, the other main risk factors for radiographic changes
include family history, some inherited and develop-
mental conditions that affect bone or joint growth or
shape, joint injuries, selected activities (such as farming
and hip osteoarthritis) and obesity (figure 4).17 However,
the balance of risk factors varies according to joint site.
For example, obesity is a very strong risk factor for knee
disease. Being obese also increases risk of both hip and
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 Seminar

hand disease (suggesting that the issue might be more

than simply mechanical), but the odds ratios of these Age
Injury
associations are much smaller from those for knee
Genetics
osteoarthritis.21,22 Similarly, the female to male ratios Predisposition Joint Overload
to osteoarthritis biomechanics
differ at different joint sites: knee disease has a much Systemic
stronger female bias than hip disease, for example. factors Instability
(eg, obesity)
There is some evidence that the risk factors for Biochemical pathways
progressive joint damage are different from those of (cytokines, proteases, and so on)
incident osteoarthritis,23,24 although the problems with
definitions and cut-off points mentioned make it
difficult to make this distinction. Bone density is a risk
factor of interest in this regard. Some data suggest a Site and severity of osteoarthritis
negative association between osteoarthritis and osteo-
porosis, even after correction for body-mass index,25 Psychosocial and Comorbidities
although this association is disputed.26 It has also been socioeconomic characteristics

suggested that although osteoporosis might protect

somewhat from getting osteoarthritis, having osteo-
porosis greatly increases the chance of progressive joint
damage if one is already osteoarthritic.27,28
Osteoarthritis has generally been thought of as a
progressive condition. Several studies suggest that this is
not necessarily the case, and that the group mean rate of
progression of joint damage from earlier studies is
affected by a few fast-progressing individuals.29–32 These
data are consistent with the fact that only a small
proportion of the huge numbers of people in the
community with osteoarthritis ultimately need joint
replacement. This point is important for clinicians,
because they can reassure their patients with early
osteoarthritis that they are unlikely to have progressive
disease.
The pathogenesis of joint damage
The tissue that has attracted most attention in relation to
the pathogenesis of this disease is articular cartilage,
largely because of the striking changes in this tissue in
advanced osteoarthritis (figure 1). The surfaces of joints
are covered by a thin layer of articular cartilage resting
on subchondral bone. Cartilage does not have nerves or
blood vessels, whereas both are plentiful in bone.
Healthy joint cartilage distributes static and dynamic
joint loading and decreases friction. Sparsely distributed
cartilage cells maintain a cartilage matrix rich in
collagen and proteoglycans. The quality of this matrix is
critical for maintaining the functional properties of the
Pain
Disability Distress
Figure 4: Schematic representation of relations between environmental and endogenous risk factors for joint
damage, osteoarthritis, and joint pain, and their consequences
subchondral bone.36,37 Subchondral bone changes could
be an important part of the pathogenesis of progressive
joint destruction,38–40 partly because the bone has far
greater ability to repair, adapt, and change the shape of
the joint than cartilage; and there might be an
association between progression and osteoporosis, as
mentioned. Whether events in cartilage precede those in
bone, are concomitant with them, or whether sub-
chondral bone changes can actually cause early cartilage
damage is uncertain.
Cytokines and other signalling molecules released
from the cartilage, synovium, and bone affect chondro-
cyte function. Osteoarthritis has traditionally been
regarded as non-inflammatory arthritis, but improved
Pain behaviour
Distress Pain
Inflammation Psychosocial factors

cartilage. Changes in the joint cartilage associated with

osteoarthritis include gradual proteolytic degradation of Cortical
the matrix, associated with increased synthesis of the Multilevel sensitisation of pathways compartment
same (or slightly altered) matrix components by the by mediators and neuromodulators
chondrocytes.33–35 These events at the molecular level
result in early morphological changes—cartilage surface
fibrillation, cleft formation, and later loss of cartilage Non-noxious Peripheral Spinal
volume. stimuli compartment compartment
Concomitant events in bone are less well understood,
but include the development of osteophytes at the joint
Figure 5: Pathogenesis of joint pain in osteoarthritis
margin, through ossification of cartilage outgrowths, Note opportunities for sensitisation and modulation of nociceptive input at
and major changes in the vascularity and turnover of the several levels.

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 Seminar
detection methods show that the inflammatory pathways
are upregulated.41 These and other clinical and
laboratory data suggest that there is a role for
inflammation in osteoarthritis, at least in some patients
and in some phases of the disease.42,43
Several of the environmental risk factors mentioned
(obesity, joint injury, joint overload) are mechanical.
Studies have stressed the importance of muscle
weakness, joint instability, and malalignment as
possible causes of osteoarthritis (previously these factors
had been assumed to be the result of the joint damage
rather than its cause).44,45 Ligamentous instability is also
an early feature of naturally occurring osteoarthritis in
the guineapig knee.46
Substantial effort is being spent in academia and
industry to explore the role of these different pathogenic
pathways in ostearthritis. With disease modification in
this condition as a goal, compounds that target
proteinases, inflammation pathways, and bone
metabolism are being tested in the laboratory, in
animals, and in clinical trials, and devices that reduce
instability or correct malalignment are also being
assessed and are in development. Implicit in the concept
of osteoarthritis disease modification is the idea that
reduction of structural joint damage will translate into
symptomatic benefits and improved quality of life. This
concept remains unproven.47
Risk factors for joint pain
Surprisingly few data are available about the risk factors
for joint pain. Most published investigations assume
that joint pathology is the main cause, and are then
concerned with the search for factors other than
radiographic changes that might explain the variance in
pain in populations. But, as Hadler48 and others have
pointed out, investigations into the epidemiology of
pain, without assuming a disease cause, are probably
worthwhile.
One review5 divided musculoskeletal pain in the
community into three main categories: spinal pain,
sprains and strains, and arthritis. Arthritis was the
commonest cause of pain in older people. Many data
relate back pain to both mechanical and psychosocial
factors.49 Similarly, risk factors for knee pain, in addition
to osteoarthritis, include various physical activities,
psychological wellbeing and health status,16 anxiety in
women,18 depression,50 hypochondriasis,51 and negative
affect (emotion).52 However, the ways in which questions
about pain are asked, and the educational level and
ethnic origin of the person being asked also affect data
on reporting of knee pain,53,54 and health-seeking
behaviours will have a major effect on which people with
pain seek medical help, complicating the subject.
The pathogenesis of joint pain
Cartilage is aneural, so whatever its role in the
pathogenesis of joint damage, it cannot be the tissue that
968
Figure 6: Hands showing florid distal interphalangeal osteoarthritis
(Heberden’s nodes)
These nodes are the common feature of so-called generalised osteoarthritis and
often become overtly inflamed.
directly generates pain. By contrast, subchondral bone,
periosteum, synovium, ligaments, and the joint capsule
are all richly innervated and contain nerve endings that
could be the source of nociceptive stimuli in
osteoarthritis.55 Imaging studies at the knee joint have
shown a correlation between pain and both synovitis
and subchondral bone changes, suggesting that these
two tissues could be sources of pain in
osteoarthritis.39,56,57 Normal joint tissues seem to be quite
insensitive to pain generation, presumably because a
low pain threshold would result in all normal
movements being painful. However, some evidence
indicates that peripheral pain sensitisation is a feature
of the osteoarthritic joint,58–60 perhaps mediated by nerve
growth factors or cytokines.61 In addition to peripheral
pain sensitisation, central pain sensitisation at the
spinal or cortical level can occur in osteoarthritis.62
Finally, the experience of pain will be modulated by
psychological, social, and other contextual factors
(figure 5).
Pain in osteoarthritis, therefore, could be due to local
and central sensitisation of pain pathways resulting in
normal stimuli becoming painful. Recent data on pain
indicate that we might also need to consider reverse
causality, since experimental data suggest that
neurogenic inflammation can contribute to joint
damage (figures 4 and 5)61 and, as noted above,
inflammation might be an important feature of the
process of osteoarthritis. Pain is accompanied by local
production of substance P and cytokines that can
interact with inflammation pathways and thereby make
a secondary contribution to joint pathology.
In summary, it is clear that any simple unitary
concept about the link between joint damage and
symptoms in osteoarthritis is untenable. We are faced
with a complex interaction between local events in the
joint, pain sensitisation, the cortical experience of pain,
and what people are doing in their everyday lives.
Context (psychosocial, economic and other factors) will
be everything in these complex interactions.
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Phenotypes, genotypes, and classification
The spectrum of joint problems and symptoms
experienced by people with so-called osteoarthritis is
very wide. Many have suggested that this condition is a
group of disorders with a similar pathological endpoint
rather than a single disease entity, and many attempts
have been made to subdivide osteoarthritis by the
number and distribution of joints affected (generalised
or localised osteoarthritis) or the presence or absence of
any obvious cause (primary or secondary osteo-
arthritis).
Debate has raged for years about the existence of the
specific disease entity of generalised, inflammatory or
erosive osteoarthritis (figure 6), and the question
remains unresolved.63–65 So-called lumpers consider this
condition part of the continuum of osteoarthritis;
splitters think of it as a separate entity. Improved
understanding of the disease means that the common
classification into primary and secondary cannot be
maintained. Osteoarthritis is a multifactorial disease
with genetic and environmental determinants. All cases
are probably affected by both genetics and
environment, with a continuous distribution between
the extremes of predominantly genetic or
predominantly environmental. For example, the risk of
post-traumatic osteoarthritis after a meniscal injury of
the knee is strongly affected by a family history of
osteoarthritis, by the presence of nodal osteoarthritis of
the hand (the classical marker of generalised
osteoarthritis), by obesity, and by sex.66–68 Also, MRI and
clinical studies show that meniscus and ligament
lesions, usually considered associated with secondary
osteoarthritis, are much more common in primary
knee osteoarthritis than was previously thought.45,69–71
Familial aggregation was first noted by Stecher for
hand osteoarthritis,72 and later confirmed for other
joints.73–76 However, familial clustering of osteoarthritis
could be explained both by genetic determinants and by
the shared environmental factors in the family, such as
dietary intake, physical activity, and occupation. The
relative roles of genetics and shared environment in
causing this disease can be assessed with a classical
twin study design, and several such studies have
confirmed a substantial genetic contribution for
radiographic knee osteoarthritis in women.77,78
However, as noted, the relation between radiographic
changes and progressive symptomatic osteoarthritis is
weak, which might question some of the relevance of
this finding. A more recent twin study79 only included
cases in which symptomatic osteoarthritis led to total
hip or knee joint replacement as the phenotype. It
confirmed the substantial genetic contribution for knee
osteoarthritis for both men and women, and extends it
to include hip osteoarthritis.
There are great difficulties in defining the real
osteoarthritis phenotype for use in genetics. The use of
self-reported pain is obviously problematic, as is the use
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Seminar
of radiographic criteria, which will miss early or
emergent disease. Joint replacement can be used, but
includes only those people with advanced osteoarthritis
who have chosen to have surgery. The complexity is
deepened by the fact that many people with clear-cut
osteoarthritis in one joint may also have the disease at
different stages of development in other joints. Perhaps
osteoarthritis should be regarded as a quantitative trait,
with phenotypic expression (based on one or several
genetic variations) of variable severity in a variable
number of anatomical locations, determined partly by
environmental influences. The expression of the
condition in any individual (presence or absence of
inflammation, pain, cartilage loss, bone formation, and
so on) might be determined by the particular mix of
genetic and environmental influence in that person.
Recent reports have identified several chromosomal
loci and gene variations associated with an increased
risk for osteoarthritis.80 Among the relevant genes are
those coding for molecules in the cartilage matrix such
as collagen types II, IX, and XI, COMP, and matrilin-3.
More recent work suggests that variations in the genes
for molecules of joint signalling or differentiation
pathways are also associated with osteoarthritis.81–83 For
example, functional variants within the gene for
secreted frizzled-related protein 3 are associated with
hip osteoarthritis in females.82 This protein is involved
in the Wnt pathway, which is critical in skeletal and
joint patterning in embryogenesis, and which might
also be a determining factor of mature adult bone mass.
Many but not all genetic variations or mutations are
associated with variable expression of the phenotypes
spondyloepiphyseal dysplasia (SED) or multiple
epiphyseal dysplasia (MED).84 Only few of the identified
loci and genes have been confirmed in more than one
population,85,86 and so far each identified gene variation
explains only a small proportion of all osteoarthritis.
Cross-population comparisons are often hampered by
use of different phenotype definitions. Much work on
genetics has so far focused on the concept of one joint,
one gene, by which it is assumed that a single
haplotype, polymorphism, or mutation is linked to an
increased risk for the disease in the hand or the hip, for
example.85,87 It is unclear to what extent this concept
holds true, or if specific genomic variations are
pleomorphic and variably influence development of
osteoarthritis in more than one anatomical site. For
either scenario, environmental effects might be key.
Continued analysis of shared and non-shared
environmental effects, and of their interaction with
each other and with genetic factors, is important for our
understanding of osteoarthritis. We need to understand
the role of a permissible environment for initiation and
phenotypic expression of the genotypic variations in the
disease. Doing so should help identify high-risk groups
and determine the role of variations in the genome
associated with osteoarthritis.
969
 Seminar
Panel: Common clinical features of osteoarthritis that
allow a bedside diagnosis to be made
Increased age
It is unusual to develop the disease before age 40 years
Pain
Use-related joint pain, relieved by rest, is one of the cardinal
features of the disease; in more advanced cases rest pain and
night pain can also develop
Stiffness
Most people with symptomatic osteoarthritis of large joints
experience short-lasting inactivity stiffness or gelling of
joints, which wears off in a few minutes with use
Reduced movement
The range of movement of the joint is often restricted, and
there is generally pain on movement, particularly at the end
of the range
Swelling
Many osteoarthritic joints develop palpable firm swellings at
the joint margin due to the formation of osteophytes; some
have minor soft tissue swelling due to secondary synovitis
Crepitus
Osteoarthritis joints often crack or creak on movement
Diagnosis and assessment
The main clinical features of the disease make it, in
general, an easily recognised clinical entity (panel).
In practice, the most common clinical problem is
differentiation of painful osteoarthritis from three other
common causes of regional or generalised joint pain in
older people: referred pain, periarticular (soft-tissue)
conditions, and somatisation (regional pain in the
absence of any local pathological cause). Pain in lower
limb joints can be referred from the spine, or from the
joint above (hip disease causing knee pain is a classic
case). Periarticular pain problems are common in all
ages, and can accompany osteoarthritis or mimic it;
common examples are trochanteric bursitis causing
apparent hip pain and anserine bursitis causing
apparent knee pain. Additionally, somatisation is a
common cause of musculoskeletal pain, especially back
pain, and clues to its presence are provided by so-called
yellow flags.88 A careful history and examination should
allow the clinician to make these diagnoses accurately.
Gauging the severity of osteoarthritis involves
assessment of both joint and patient. This assessment
may be done in the clinical setting in support of
diagnosis, treatment decision, or evaluation of treatment
response. The clinical examination of the osteoarthritic
joint can be helpful in assessing the extent of joint
damage, such as deformity and instability, but the
reproducibility of findings is low.23 Radiographic
examination is often done in support of the clinical
970
diagnosis of osteoarthritis, but in view of the poor
correlation between clinical problems and pain, the
value of such an examination is debatable. The
radiograph can do harm, because it may convince a
person that they have degeneration of their joints, when
in fact the radiographic changes are irrelevant to their
problems. However, such examinations with standard
methods provide important information for the surgeon
if an intervention such as osteotomy or joint replace-
ment is being considered.
Many disease-specific questionnaires have been
developed and validated for standardised assessment of
symptoms, function, and disability in osteoarthritis.89
Some of these instruments are useful in a routine
clinical setting, and might also be used for cost-utility
estimates.90 Other instruments are more extensive and
only appropriate for research. The validity of any
instrument for the particular patient group (and joint) to
be studied must be considered before making a choice.
For example, the addition of new modules in the
questionnaire “knee injury and osteoarthritis outcome
score” (KOOS)91 to an already well tested instrument
such as the Western Ontario and McMaster Universities
osteoarthritis index (WOMAC)92 improved its respon-
siveness when applied to patients with knee osteo-
arthritis, who have higher expectations and are more
active than those for which WOMAC was originally
designed (www.koos.nu).
Principles of management
Several reviews and guidelines on the management of
osteoarthritis exist, based on evidence from trials about
Severe
Surgery
partial or total Few
joint replacement
and
Surgery
(joint preserving)
osteotomy, resurfacing
Supervised Some
Advanced
non-surgical interventions
injections
Simple non-surgical interventions,
non-steroidal anti-inflammatory drugs,
other drugs, physiotherapy or occupational
therapy, orthoses, other aids
All
Self help
simple analgesics, topical agents,
lifestyle, nutraceuticals
Mild
Information and advice
education, weight loss, exercise, lifestyle alterations
Numbers of people
Figure 7: Principles of the management of osteoarthritis
Suggested sequential, pyramidal approach to disease management.
www.thelancet.com Vol 365 March 12, 2005

the effectiveness of the various interventions
available.47,93–95 We do not intend to review these data, but
rather outline some general principles that we believe
are important for good management of people with this
condition.
Although symptomatic osteoarthritis is very common
in the community, much of it is mild, and progression to
severe disease is fairly uncommon. Moreover, it is clear
that many elderly people regard musculoskeletal aches
and pains and stiffness as a normal part of the aging
process, rather than a disease.96 Many never seek
medical help. We believe that it is important not to
overtreat those who do seek help and advice, and that it
is inappropriate to medicalise most of those with mild
osteoarthritis.
Having said that, many of those who do consult a
doctor lead lives that are disrupted by the pain, disability,
and distress that accompany their osteoarthritis. It is
important that their management centres around a
careful assessment of the severity of those patient-
related outcomes and not of the severity of joint damage
(unless orthopaedic surgery is being considered).
Figure 7 presents a sequential, pyramidal approach to
the management of osteoarthritis. All patients should be
given general advice about the disease, lifestyle
alterations that might reduce symptoms, the need to
keep fit and active, and the need to lose weight if they are
obese. Referral to allied health professionals can help
with delivery of educational and exercise-based
interventions, although more and better research is
needed about these modalities of treatment, which have
not always produced major benefits in previous trials.97
Additionally, all patients should be empowered to take
control of the condition themselves through self-help
measures with proven effectiveness, such as use of
simple analgesics and topical agents as well as some
nutraceuticals. Only if these measures fail should
interventions that require medical supervision, such as
non-steroidal anti-inflammatory drugs, physiotherapy,
and the use of aids and appliances be considered.
Towards the top of the pyramid, for those in whom other
measures have failed, are the more invasive inter-
ventions. For those with severe osteoarthritis, joint
replacement is very effective.
One of the major problems with the practice of
evidence-based health care for people with osteoarthritis
is that the evidence only concerns single interventions,
whereas in practice combinations of different inter-
ventions and packages of care involving a mixture of
pharmaceutical and non-pharmaceutical treatments are
used. We believe that such packages can be very helpful
for people with symptomatic osteoarthritis, but this
notion remains unproven.
Given the huge economic and personal burden of
osteoarthritis, and the fact that it is the main cause of the
increasing need for joint replacements,98 we need to
consider prevention. Some of the major risk factors for
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Seminar
joint damage are potentially modifiable and, in theory,
the rate of obesity and joint injury could be reduced.
However, such reductions are unlikely to happen;
indeed, both obesity and injury seem to be on the
increase, despite knowledge that they are detrimental to
health.
Conclusions
Osteoarthritis is an increasingly important public-health
problem.99,100 Over recent years good progress has been
made in our understanding of many of the associations
and pathogenic pathways responsible for both the pain
and joint damage. As a result, we can develop theoretical
strategies for primary prevention of joint damage,
through reduction of obesity and joint trauma in
particular, but these strategies seem unlikely to decrease
osteoarthritis in the short term.47 Therefore, more
research is needed about secondary prevention of
progressive joint damage and about control of pain.
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