Osteoarthritis (OA) is by far the most common form of joint disease throughout the world.

It is strongly associated with age, and extremely common in older people; some studies
estimate that over 80% of people over 55 years of age have osteoarthritis of at least one
joint. It mainly affects the hips, knees, spine, hands and feet. Hip and knee OA are the most
important because of the high prevalence of pain and disability that they cause in older
adults, and the massive healthcare resource input that results from this, particularly in terms
of the provision of joint replacements.

The disease processes leading to OA result in a final common pathway of joint failure akin
to heart or kidney failure. Clinically OA, or joint failure, is a very heterogeneous condition,
but is the end result of biochemical and mechanical insult that exceeds the joint’s ability to
repair itself. Classification and subtyping are difficult. In the past people have tried to
subset OA according to whether or not there is an obvious cause (primary versus secondary
OA), whether symptoms are associated with joint damage or not (asymptomatic versus
symptomatic OA), the extent and pattern of joint involvement (e.g. localized versus
generalized OA), the type of bone reaction (hypertrophic versus atrophic OA), and whether
the disease process is active, resulting in progression, or not (progressive versus inactive
OA). Here we prefer to classify OA into two main categories – what has been called
‘sporadic’ or ‘common-or-garden OA’ – by far the most frequent type, with its varying
degrees of joint involvement (distribution), joint damage, and impact on peoples’ lives, and
‘atypical forms of OA’ that include joint failure that can result from a number of clear
antecedent causes, and a variety of relatively unusual manifestations of joint failure.

We have therefore divided this chapter into three parts: first a description of joints and how
diseases can affect them, then a discussion of ‘common-or-garden’ OA, and finally a brief
description of some of the atypical variants of OA.

Joints occur where two or more discrete bones meet each other in the body. These joints
can be fixed or can allow movement between the bones. There are three main types: fibrous
joints, cartilaginous joints and synovial joints.

Fibrous joints join bone or cartilage by fibrous tissue and allow very little movement, such
as in the sutures of the skull. Primary cartilaginous joints are between bone and hyaline
cartilage. In secondary cartilaginous joints the two bone ends are covered in a thin layer of
hyaline cartilage and these two ends are joined by interposed fibrous cartilage. An example
of this is the symphysis pubis. The spine consists of a series of fibrocartilaginous joints as
each vertebra is joined to its neighbour by an intervertebral disc consisting of fibrocartilage
filled with gel. Even in cartilaginous joints that allow very little movement the joint can
fail, particularly if subjected to heavy loads such as the acromioclavicular joint in
weightlifters. Damage to the fibrocartilage can sometimes be accompanied by osteophyte
formation. This can be thought of as a variant of OA. However, OA is usually defined as a
condition of synovial joints.

Synovial joints (see Figure 5.1) have evolved in order to allow movement between bones.
The adjoining bone ends are covered by extremely smooth hyaline cartilage (see Figure
5.2). This junction is enclosed within a joint capsule containing synovial fluid which bathes
and lubricates the hyaline cartilage. The capsule is lined by a synovial membrane that
contains cells called synoviocytes. These produce lubricant and hyaluronic acid which is
responsible for viscosity of the synovial fluid. They also produce cytokines and growth
factors and remove unwanted waste products, such as metabolites, from the synovial fluid.
The capsule is reinforced by ligaments. These are arranged in such a way as to provide
stability throughout the range of movement of the joint. Some synovial joints have intra-
articular discs of fibrocartilage. The hip has a ridge of fibrocartilage called the labrum
which deepens the articulation, whilst in the knee the same tissue has migrated further into
the joint and has become the menisci. The menisci spread load through the knee and
improve congruence, thereby improving stability. They thus protect the hyaline cartilage
from both compressive and shear forces. Synovial joints move in a controlled way because
of the muscle forces that act across them. Muscles are attached to bone by tendons.
Ligaments attach to bones in a similar way. These areas of attachments by soft tissues to
bone are called entheses and are subject to tensile forces.

All of the structures that compose synovial joints can fail and lead to the final common
outcome of OA. Once one structure begins to fail, the surrounding structures are affected
adversely and then also fail. Normally the insult, whether biological or mechanical, affects
a number of structures simultaneously and the remaining structures secondarily. For
example, a traumatic knee injury could lead to a tear of the meniscus, fracture of
subchondral bone, disruption of the hyaline cartilage and stretching of entheses, all
occurring simultaneously.

Subchondral bone supports the overlying hyaline cartilage. It is susceptible to fracture

when subjected to great compressive force or to avascular necrosis when subjected to shear
forces. Collapse of the subchondral bone leads to splitting of the overlying hyaline
cartilage. Synovium can become inflamed due to chemical irritants such as crystals, or
infection; additionally, the synovium is prone to inflammation resulting from systemic
immune-related problems, as in rheumatoid arthritis. Synovitis of any cause results in the
release of inflammatory mediators such as cytokines, and affects the production of
hyaluronic acid, thereby altering the viscosity of the synovial fluid. The cytokines in the
synovial fluid affect the catabolic and anabolic activities of the chondrocytes and
osteocytes in the nearby cartilage and bone, as well as the capsule, leading to alterations in
the normal integrity of these tissues, rendering them more susceptible to mechanical
insults. The entheses are commonly stretched by injuries producing inflammation and
oedema in the adja- cent bone; they are also susceptible to inflammation in the seronegative
spondarthropathies, such as ankylosing spondylitis. The menisci or the labrum are
susceptible to tearing under excessive shear forces. Once their function is compromised,
the hyaline cartilage can become exposed to abnormal load and can fail.

Failure of hyaline cartilage results in the subchon- dral bone being subjected to both
increased load and direct pressure from synovial fluid. The final common pathway of all
of these mechanisms is damage to hyaline cartilage, increased load on the underlying bone,
cyst formation due to penetration of the subchondral bone by synovial fluid under pressure,
and new bone formation on the joint margins (osteophytes), i.e. the development of
osteoarthritis (OA). OA, therefore, can occur as a result of any form of joint disease.

Osteoarthritis (OA or joint failure) is relatively easy to define pathologically, being

distinguished by focal areas of loss of articular cartilage within a synovial joint,
accompanied by sclerosis of the underlying bone, and varying degrees of change in other
joint tissues.

This pathology is reflected in characteristic changes in images of joints, particularly the

plain radiograph, which is used to identify the pathology. This pathology is seen in most
of the higher animal species, and it is the final common pathway of many forms of joint
insult or injury; it is particularly common in some synovial joints in older humans. The
pathology of OA is sometimes, but certainly not always, associated with the development
of joint pain and other symptoms and signs, but it is difficult to describe or define clinical
OA. This is the central dilemma of OA: pathological changes of OA are very common in
older people, but often asymptomatic; joint pain is very common in older people, and
sometimes due to OA. This means that clinicians need to think carefully about the cause of
joint signs and symptoms in older people, before immediately labelling them as being due
to OA on the basis of age or a radiographic appearance.

Prevalence and distribution

Most of the available data on the prevalence of OA comes from the developed Western
world, and most of it is based on a radiographic definition of the condition, rather than a
pathological or clinical one.

The joint sites most commonly involved are the knees, hips, hands, feet and spine. OA
affects focal areas within joints: early in the disease only a localized area is affected,
although later on it may spread to affect the whole joint. The sites most commonly affected
in the knee are the anteromedial compartment of the tibiofemoral joint, and the lateral facet
of the patellofemoral joint, in the hip it is the superolateral aspect that is most often
damaged, and in the hands and feet it is the terminal (distal) interphalangeal joints, as well
as the first MTP and thumb base that are most often involved.

Increasing age is a strong risk factor, and there are differences in prevalence and
distribution in men and women. Figure 5.3 illustrates the overall prevalence in Western
men and women of hip, knee and hand OA.

Some racial/ethnic differences exist in the prevalence and distribution of OA. For example,
superolat- eral hip OA, which is very common in Caucasians, is relatively uncommon in
people of Chinese origin. As explained later, this may be due to subtle differences in
skeletal shape.

Aetiology and risk factors

OA has no single cause; rather, it is due to a variable combination of several risk factors
affecting different individuals and different joint sites, which explains its heterogeneity.
OA arises as a result of a mixture of both systemic predisposition and local biomechanical
risk factors, as shown in Figure 5.4, and Box 5.1 shows the major risk factors currently
known.

GENETIC PREDISPOSITION

From twin studies and other data, it has been esti- mated that about 40% of the
predisposition to OA may be genetic. However, there is no ‘OA gene’; rather, several
different sites within the genome each confer a small increased risk. Many of the sites
associated with this increased risk relate to genes important for skeletal development,
adding to other evidence that suggests that bone size and shape are important determinants
of the likelihood of getting OA.

AGE

OA is strongly associated with increasing age. But this is not because age-related changes
in joints are similar to those of OA – there are major differences in the ‘pathology’ of
ageing joints from those of OA, and it has been suggested that we would need to live for
over 200 years before the age-related changes in the joints alone (such as thinning of the
cartilage) would cause OA. The association with age may have more to do with joint
stability and muscles than joints. As we age, our cartilage gets thinner and our muscles get
weaker, and the stability of major joints such as the knee may be affected in subtle but
important ways by these changes. Some studies have suggested that muscle weakness
precedes the development of knee OA.

GENDER

As shown in Figure 5.3, there are differences in prevalence of OA between men and
women. The reasons for this are not clear. Changes related to the female menopause appear
to be particularly important, as knee OA prevalence in women rises sharply after the
menopause, and inflammatory OA of the hands often starts during the menopause.

DIET AND OBESITY

Obesity is a strong risk factor, particularly for knee OA. It is also a risk factor for increased
incidence of hand OA, suggesting that it may have some systemic influence, perhaps
through changes in obesity-related biochemical factors such as leptin levels. In addition,
there have been a number of studies to suggest that
some vitamin deficiencies may be important in the development of OA, including vitamins
C, D and K.

ABNORMAL JOINT SHAPE AND SIZE

Joint shape is an important risk factor, particularly for hip OA. Hip dysplasia predisposes
you to hip OA in later life, and more subtle abnormalities of the size or shape of the head
of the femur or acetabulum (such as the shape changes that cause femoroacetabular
impingement – FAI), may be responsible for much of the common-or-garden hip OA seen.
The differences in shape of hips in Chinese from that in Caucasians may explain the low
prevalence of hip OA in Chinese people. It is possible that joint size and shape are also
important in knee OA.

PREVIOUS INJURY

Injuries that affect the shape or stability of a joint predispose to OA. This is most apparent
in joints which have a low prevalence of ‘common-or-garden’ OA such as the wrist or
ankle – OA at these sites is usually due to a previous significant injury. At the knee joint,
meniscal and ligament injuries, particularly ACL rupture, are important predisposing
factors for OA.

NEUROMUSCULAR PROBLEMS

Severe neurological problems of specific types can lead to the important variant of OA
called ‘Charcot’s joints’. Lesser forms of neurological change, including weak muscles,
and loss of proprioception, may be important in ‘common-or-garden’ OA. In addition, joint
laxity seems to predispose to OA. Conversely, spasticity results in very tight joints
accompanied by abnormal joint loading leading to joint damage and secondary
osteoarthritis. OA of the hip is particularly common in persons suffering from spastic
cerebral palsy.

JOINT LOADING, OCCUPATION AND OBESITY

The extent to which normal or excessive joint use, including exercise, are risk factors for
OA, or alternatively protective to the condition, is a contentious issue, and we do not yet
understand exactly what aspects of joint loading matter most to joint health. However,
certain specific occupations involving repetitive ‘overuse’ of joints can predispose to OA,
resulting in special forms of the condition such as ‘picca-thumpers thumb’ (OA at the base
of the thumb in people who spent their working days shifting printing blocks around with
their thumbs). The fact that obesity is particularly important for knee OA indicates that a
part of the risk is likely to be due to loading factors, as well as any systemic influence.

BONE MINERAL DENSITY

Long ago it was noted that people who came to hip replacement because of fractures caused
by osteo- porosis were unlikely to have hip OA. Subsequent studies have confirmed that,
at both the knee and the hip, high bone mineral density is a risk factor for OA, and low
bone mineral density is protective. It is not understood how these relationships operate, and
it is unclear to what extent this is a systemic factor, or whether it is about local loading of
cartilage and subchondral bone.

Pathology and pathogenesis

The OA process is mechanically driven but chemically mediated.

PATHOLOGY

The key pathological features of OA are shown in Table 5.1, which also documents their
radiographic correlates.

Historically, pathologists and academics interested in OA have concentrated on the

changes seen in articular hyaline cartilage, more than the changes in other joint tissues. The
cartilage changes include: early softening and swelling or articular cartilage, with an
increase in its water content; intermediate fragmentation and fissuring of the cartilage
surface; and late erosion down to the underlying bone (see Figure 5.5). This pathology is
very well described, and several classification and scoring systems are available. The
Outerbridge classification is most commonly used by orthopaedic surgeons. It originally
described changes to the articular surface of the patella, but it is now used in all synovial
joints, particularly as arthros- copy is now common and allows direct visualization of many
joints.

Grade 1 Softening and swelling of the cartilage

Grade 2 Fragmentation and fissuring of the cartilage in an area less than 1⁄2 inch in
diameter

Grade 3 Fragmentation and fissuring of the car- tilage in an area more than 1⁄2 inch in
diameter

Grade 4 Exposure of underlying bone.

The cartilage changes are accompanied by extensive changes in the tidemark between bone
and cartilage, with vascular invasion and extension of the calcified zone, as well as
thickening of the subchondral bone. At the margins of the joint, periosteal cells proliferate
and change their phenotype to form bone (osteophytes). In addition, there is usually some
synovial inflammation, which may result in joint effusions, as well as thickening and
fibrosis of the joint capsule, which may be extensive. In advanced cases the damage to the
subchondral bone can lead to the formation of cysts, and loss of bone volume. All of these
changes vary in extent in different individuals, and there are also some differences
according to joint site, with, for example, unusual pathological features such as hyaluronan
cyst formation being a feature of some hand OA.

The radiograph is a blunt instrument for revealing these pathological changes, but it is the
only routinely available tool to detect them, and as long as the changes in the joint are
severe enough, they result in characteristic joint space narrowing, osteophyte formation
and subchondral bone sclerosis, which are pathognomonic of OA (see Figure 5.6). As with
the pathological changes, there are a number of different scoring systems available to
assess the severity of radiographic changes. The one used most commonly is the Kellgren
and Lawrence scoring system, which divides OA X-ray changes into five categories:

0 Normal 
 No features of OA

1 Doubtful 
 Minimal osteophyte, doubtful significance

2 Minor 
 Definite osteophyte, no loss of joint space

3 Moderate 
 Some diminution of joint space

4 Severe 
 Advanced joint space loss and sclerosis of bone

PATHOGENESIS

As already explained, the OA process is initiated by a mixture of systemic predisposing

factors interact- ing with local mechanical influences that affect the site and severity of the
OA changes, but the changes themselves are chemically mediated.

There are many different hypotheses about how the process is mediated. As with OA
pathology, research on OA pathogenesis has been dominated by work on articular cartilage
rather than other tissues, although it is now seen as a disorder of the whole synovial joint
organ.

A lot of current work revolves around the generation of local cytokines and proteolytic
enzymes within the joint, and cell signalling pathways that link chondrocyte activity to
changes in the subchondral bone, synovium and capsule. The main emphasis of much OA
research remains on trying to understand how sparsely distributed cells in cartilage
(chondrocytes) maintain the integrity of the articular cartilage in normal joints, and the
anabolic and catabolic processes that result in OA. The early changes in cartilage appear
to result from collagenase enzymes disrupting the integrity of the type II collagen matrix
which encloses the hydrophilic proteoglycans, leading to swelling and softening;
subsequently, more proteolysis and damage to proteoglycans, as well as collagen, results
in the fissuring and loss of volume. It is less clear how the changes at the tidemark and in
subchondral bone are mediated, where increased calcification and angiogenesis are
switched on, and trabecular thickening is seen, perhaps in part as a result of subchondral
micro-fractures of trabeculae (see Figure 5.7).

One of the problems encountered by those studying OA is to detect it in its earliest stages,
before the pathology is severe enough to become apparent on an X-ray or be clinically
relevant. Animal models of the condition help here, and there has been interest in what
comes first – changes in the cartilage, bone, synovium or other parts of the joint? The
evidence, not surprisingly, is that they occur together and are linked and, contrary to earlier
ideas, it is apparent that changes in the bone and soft tissues can occur in the earliest stages
of the process in humans. However, the OA process and the homeo- stasis of the normal
synovial joint are yet to be well understood.

NATURAL HISTORY AND OUTCOMES: INCIDENT-VS-PROGRESSIVE OA

In the past OA has been talked about as a degenerative condition, a progressive one, and
some- thing that cannot get better. None of these ideas is correct. It is not a degenerative
process; rather, the changes that are going on in cartilage and other tissues are very active
ones. The term ‘degenerative joint disease’ should be avoided as it conveys old age,
inevitability and negativity to both patients and healthcare professionals alike. Similarly,
OA is not necessarily progressive. Natural history and physiological imaging studies (such
as bone scintigraphy) suggest that it goes through periods of activity and quiescence. Thus
a joint may be mechanically compromised in a susceptible person, and respond by
activation of the OA process, leading to some changes to cartilage and bone, and the
characteristic radiographic changes. This may result in the process then becoming
quiescent for long periods of time, although physical examination and radiographs of the
joint will still reveal the changes of OA. There is some evidence that the risk factors for
progression are a little different from those for initiation of the process – for example,
malalignment of a joint is more important for progression of OA than for initiation.

Clinically, it is also clear that patients can have periods of more severe symptoms, followed
by quiescent periods, and in a significant proportion of cases (probably about 30%) time
results in clinical improve- ment rather than deterioration.

Repair of the pathological changes is less common but can occur: spontaneous
improvement in hip OA is well described, as is joint repair in response to major mechanical
treatment interventions, such as osteotomy at the knee, or mechanical unloading by use of
Ilizarov frames for ankle OA. However, the repaired OA joint is not normal, as the hyaline
articular cartilage is replaced by fibrocartilage.

Symptoms and signs

Pain is the main clinical problem. But, as already noted and shown in Figure 5.8, there is
a poor correlation between the radiographic evidence of OA in joints, and the prevalence
of the clinical symptoms such as pain.
The most common symptoms and clinical signs reported by/seen in people with clinical
OA are documented in Box 5.2.

PAIN

Most people with clinical OA report discomfort or pain in or around the joints affected, but
their pain experiences vary hugely, both over time, between individuals, and, as outlined
further below, according to the joints affected. It is very common for patients to have
trouble describing their pain. They often refer to the sensation as a deepseated discomfort
similar to a toothache emanating from within the joint. Reported experiences vary from: a
dull ache after exercise; through to the more common moderate, activity related pain; to
excruciating, continuous pain and pain at night. Severe pain that wakes the patient nightly
is a particularly debilitating symptom of severe arthritis and leads to sleep deprivation.
Many people report that no two days are the same, the pain experience being variable and
seemingly inexplicable.

We do not know why OA sometimes causes pain. There are no nocioceptive receptors in
the cartilage, which is the major tissue affected pathologically, but nocioceptive pathways
do occur in subchondral bone, in periosteum and in the synovium and capsule of the joint.
It would appear likely that some of the variation in the pain experience is related to
differences in where the nocioceptive drive is coming from in different people/joints; there
is good evidence for bone being a major source of pain in advanced knee OA, but in other
sites/severity, it may be different (see Figure 5.9).

In addition to there being a nocioceptive drive to cause pain, pain amplification systems,
both locally in the joint and within the central nervous system, can contribute to the pain
experience in chronic OA. Once pain has become chronic, amplification pathways can be
activated locally and at both spinal and cortical levels, leading to chronic and more
widespread pain, which is difficult to treat, particularly if accompanied by mood changes.
Anxiety and depression both affect the perception of pain and its response to interventions.

OTHER SYMPTOMS

Stiffness, or gelling of the joint after inactivity, is a classical feature of OA, resulting in
people having difficulty getting moving after resting. This is particularly common in the
early morning after first awakening. The cause is not known. Less well-appreciated
symptoms of OA include fatigue, sleep disturbance caused by pain and anxiety/depression.
Each of these is very common, and can have a big impact on individuals, and, as discussed
below, may need management separately from any attempt to deal with joint damage or
pain.

SIGNS

On examination the joints affected may appear swollen, there may be evidence of wasting
and weakness of surrounding muscles (as in quadriceps muscle wasting at the knee, or the
Trendelenburg sign at the hip which signifies weakness of hip abductors) and, in advanced
OA, joint deformity. Palpation may reveal bony swelling at the margin of the joint, signs
of mild inflammation, such as heat over the joint line, and an effusion. On movement there
is usually a reduced range, with pain at the end of the range, and crepitus may be felt as the
joint is moved; in advanced disease instability may be detected.

As emphasized in this chapter, the challenge for the clinician is to ascertain whether the
symptoms and signs are the result of OA or of some other articular or periarticular problem.

SYMPTOMS AND SIGNS AT DIFFERENT JOINT SITES

Hips Pain is usually felt in the groin, laterally over the hip and radiates down the
anterolateral aspect of the thigh to the knee. Occasionally the pain can radiate beyond the
knee. Referred pain felt only in the knee is not uncommon, and clinicians should always
consider hip OA as a cause of isolated knee pain. Pain is worse on exercise and walking
distance is reduced. Pain at rest and night pain can be particularly troublesome. Stiffness
is usually experienced first thing in the morning and after having sat still for a while, but it
quickly resolves on movement to be replaced by pain. Complex movements, such as getting
in and out of a motorcar or putting on socks, which involve deep flexion combined with
rotation, are often difficult or impossible to perform. Patients struggle with stairs and in the
absence of a banister may only manage stairs on all fours.

Examination reveals an antalgic gait, characterized by an uneven cadence, in which less

time is spent in the stance phase of the painful limb. There is a globally reduced range of
movement with internal rotation often restricted early in the disease progression. Joint
move- ment is limited by pain at the extremes of movement.

Knees Knee osteoarthritis occurs most commonly in the medial tibiofemoral joint but can
occur in all three compartments and is often tricompartmental. Isolated patellofemoral OA
is probably due to altered biomechanics of the extensor mechanism. Pain is felt glob- ally
over the knee and the proximal tibia. In isolated patellofemoral OA the pain is felt
anteriorly over the knee and is often worst when ascending or descending stairs as the
patella is compressed against the femur. As in the hip, the pain is a deep-seated aching
sensation related to exercise. Rest pain and night pain develop in the later stages of the
disease. Patients sometimes report audible crepitus (crackling or grating sounds) coming
from the knee as well as symptoms of instability (a feeling that the knee is going to give
way). They may notice gradual deformity of the knee, in particular varus deformity (see
Figure 5.10), but less commonly valgus deformity. Fixed flexion deformity means that the
knees cannot lock in full extension and thus patients cannot stand comfortably for
prolonged periods due to muscle fatigue. Loss of flexion beyond 90 degrees makes
standing from a sitting position difficult as patients cannot move their centre of gravity
anterior to their mid-coronal plane. Swelling and stiffness are common features.
Examination reveals an antalgic gait, wasting of quadriceps muscles, joint effusion, joint
deformity, and crepitus palpable and sometimes audible on movement. The joint deformity
may be passively correctable. Deformity is towards the compartment most severely
affected, usually varus deformity with predominantly medial compartment OA. There is
sometimes tenderness along the joint line and palpable osteophytes that can be tender.

Hands The joint sites commonly affected in the hand are the distal interphalangeal joints
(DIPs) and the thumb base (both the radiocarpal and scaphotrapeziod joints); less
commonly, proximal interphalangeal joints and metacarpophalangeal joints are also
involved (see Figure 5.11).

OA of the hand is strongly associated with OA at other joint sites, especially the knee, and
with genetic predisposition to OA, suggesting that it is a feature of generalized ‘common-
or-garden’ OA, but it has several unique pathological and clinical features, not often seen
at other sites. It is far more common in women than in men and often starts relatively
abruptly around the time of the menopause (sometimes called ‘menopausal OA’) with
painful inflammation in the distal interphalangeal joints: over time (years) the inflamma-
tion settles and the joint is left with the typical pathological features of OA. Erosions can
occur (‘erosive OA’), and cysts containing hyaluronan that protrude at the margins of the
joints are not uncommon. Distal interphalangeal joint OA is not generally a major problem
in terms of function, but thumb base OA can be, as it leads to instability and difficulty with
pinch grip.

Other joints Almost any joint can be affected by OA, particularly if it is damaged by severe
trauma. However, there are peculiarities to the phenotype of the condition at different sites.
For example, elbow OA is almost always asymptomatic (just causing loss of full extension
of the elbow), while shoulder OA is more likely to result in severe bone destruction (a con-
dition sometimes called ‘Milwaukee shoulder’) than is OA at other joint sites.