British Columbia Medical Journal, October 2010 issue: Clinical features and pathogenetic mechanisms of osteo - arthritis of the hip and knee

Manal Hasan, MBBS, MD, Rhonda Shuckett, MD, FRCPC, Diplomate ABIM

Clinical features and patho-
genetic mechanisms of osteo-
arthritis of the hip and knee
Understanding how osteoarthritis develops is critical to treating this
disabling disease.

steoarthritis (OA) is a non- tween X-ray findings and symptoms

O
ABSTRACT: Osteoarthritis is a non-
inflammatory form of arthritis that inflammatory form of arth- of OA.1
accounts for 25% of visits to primary ritis. A common miscon- OA accounts for 25% of visits to
care physicians. When osteoarthritis ception is that OA is due primary care physicians, and 50% of
affects the hip and knee, it can lead solely to wear and tear, since OA is NSAID prescriptions.2 It is estimated
to major disability and compromised typically a disease of persons in the that up to 80% of the population will
quality of life. Diagnosis relies on sixth decade and beyond. “Degenera- have radiographic evidence of OA by
clinical symptoms, physical find- tive arthritis” is often used as a syno- age 65, with 60% of those showing
ings, and radiographic findings. The nym for OA, but OA is not the result of symptoms and thereby having clinical
interplay between mechanical and a bland degenerative process; rather, OA.3 Another study found that by age
systemic factors such as congenital OA involves both degenerative and 70 to 74 years, about 33% of men and
abnormalities, obesity, and malalign- regenerative processes. 40% of women will have OA with
ment may predispose individuals to OA is common and serves as the clinical and X-ray features.4 The life-
osteoarthritis of the hip and knee. main source of chronic joint com- time risk of developing symptomatic
We must identify these factors and plaints in adults. The morbidity con- knee OA is about 45%, rising to 66%
the underlying causes of osteoarth- ferred by OA of the knee and hip in an in obese persons. While there is vari-
ritis if we are to develop more pro- ever-aging population is major. Its ation in these numbers, it is clear that
gressive early interventions for this high prevalence and huge impact on the morbidity and disability conferred
common affliction. quality of life demand that we engage by OA of the hip and knee is enormous
in better understanding of OA by con- and demands our attention.5
sidering diagnostic, epidemiological,
clinical, and radiographic features. An Symptoms and
understanding of how OA is classified physical findings
and OA risk factors is also critical. The main symptoms of OA of the knee
or hip are pain, stiffness, and altered
Diagnosis and function. Initially this tends to be
epidemiology worse with weight bearing and ambu-
The diagnosis of OA relies on clinical lation. Eventually this can progress to
symptoms, physical findings, and
radiographic findings. Not all persons Dr Hasan is a rheumatology fellow in the
who have radiographic OA have clin- Division of Rheumatology at the University
ical disease. Conversely, not all per- of British Columbia, sponsored by the King-
sons who have joint pain demonstrate dom of Saudia Arabia. Dr Shuckett is a clin-
plain radiographic findings of OA. ical associate professor in the Division of
Thus, there is often discordance be- Rheumatology at UBC.

www.bcmj.org VOL. 52 NO. 8, OCTOBER 2010 BC MEDICAL JOURNAL 393

Clinical features and pathogenetic mechanisms of osteoarthritis of the hips and knees

pain day and night once cartilage loss al compartment OA of the knees. Less
leads to bone-on-bone contact. True commonly, patients may present with
hip pain is felt in the groin most com- a valgus or knock-knee deformity,
monly, but can also present in the but- indicative of more advanced disease
tock and often down the anteromedial in the lateral compartment of the knee.
thigh to the knee. Not uncommonly, On occasion, and much less common-
patients may present solely with knee ly, patients may present with isolated
pain when the problem is in the hip. OA in the patellofemoral joint, which
Pain arising from osteoarthritis of the can of itself be very symptomatic.
knee is felt right around the knee joint, In the case of the hip, a true cap-
and unlike pain caused by hip OA, this sular pattern of limitation is found
pain does not typically radiate. with groin or buttock pain (or both)
In contrast to inflammatory arthri- and particular pain with internal rota-
tides such as rheumatoid arthritis, with tion of the hip. Flexion deformity of
their prolonged morning stiffness and the involved hip can be present with
worsened pain in the morning, OA advanced OA. Patients will often walk
Figure 1. Radiograph of osteoarthritis of tends to worsen as the day progresses. with a limp, and a waddling Trende-
the hip showing predominant superolateral The stiffness in OA is termed “inac- lenburg gait may be evident in late
joint space narrowing, subchondral
sclerosis of whitening of the bone adjacent tivity stiffness” and contrasts with stages.
to the joint space, and some marginal the prolonged “morning stiffness” of
osteophytes. rheumatoid arthritis. Inactivity stiff- X-ray findings
ness in osteoarthritic lower limb joints Standard knee X-rays should include
lasts about 5 to 10 minutes and occurs a standing anteroposterior (AP) view
when the patient gets up and bears of both knees, plus lateral views. In
weight after prolonged immobility. patients with suspected posterolateral
On physical examination, a small OA with a mild valgus deformity, a
effusion with a fluid bulge sign can be 30 degree flexed standing posteroan-
present in OA of the knee. Larger effu- terior (PA) view with the beam
sions can occur but are less frequent directed 15 degrees from cephalad to
than in the inflammatory arthropathies. caudad may be valuable in showing
Synovial fluid analysis after aspira- the disease in the posterior aspect of
tion of an OA knee effusion reveals the lateral compartment of the knee.6,7
that the fluid is thick and viscous with In early cases, a standard standing AP
a low synovial white blood cell count, view may appear normal or indicate
most of which are mononuclear cells. very mild OA, whereas the standing
On examination, there may be carti- flexed PA view may show bone-
laginous crepitus or a crackling feel- on-bone contact. Patellofemoral OA
ing on palpation of the knee with mo- of the knee cap is also a common
tion. Eventually there may be coarse finding, best diagnosed on a skyline
bone-on-bone crepitus whereby the X-ray view.
opposing bone ends, denuded of carti- X-rays of the hips to evaluate for
lage, seem to grate against one anoth- OA should include a standing AP
er. There is often a loss of range of pelvis view and frog-leg views of the
motion of the involved knee or hip, suspected hip joint. It is important to
Figure 2. Medial compartment particularly with progression of OA. always order standing X-rays of both
osteoarthritis of the knee with medial Loss of cartilage of the knee can knees in the case of suspected knee
compartment joint space loss.This marked
narrowing is between the medial tibial
lead to malalignment of the leg with a OA and an X-ray of the pelvis and not
plateau and the medial femoral condyle. varus deformity or bow-legged posi- just the affected hip in the case of sus-
The fibula can be seen in its lateral tioning of the leg being evident. This pected hip OA. This will allow for
location.
angulation of the knee applies to medi- comparison between sides and im-

394 BC MEDICAL JOURNAL VOL. 52 NO. 8, OCTOBER 2010 www.bcmj.org


proves the ability to diagnose mild to application. MRI has emerged as an Table 1. Traditional classification of OA
moderate disease. excellent modality for detection of OA
On plain X-ray evaluation, loss of when the plain radiographs indicate Primary osteoarthritis
the radiolucent cartilage, termed joint no disease or mild disease, and the • Idiopathic
space narrowing, is seen in OA. In the patient’s symptoms are out of keeping • Generalized
hip joint the joint space narrowing with the apparent severity of disease. • Erosive
tends to be more in the weight-bearing MRI can detect large focal articular
Secondary osteoarthritis
superolateral aspect of the joint, again cartilage lesions that cannot be detect-
• Due to mechanical incongruity of joint,
highlighting the role of mechanics in ed on plain films.6-8 congenital or acquired (e.g., acetabular
OA ( Figure 1 ). However, there are dysplasia of hip or internal knee
different patterns of OA of the hip, and Classification of OA derangement)
it is possible to get more central wear, Traditionally OA has been classified • Due to prior inflammatory disease (e.g.,
rheumatoid arthritis)
particularly in patients with deep sock- as primary or secondary ( Table 1 ).9
• Due to endocrine disorders (e.g.,
ets or protrusio acetabuli. In the knee, Primary OA denotes generalized or diabetes, acromegaly)
main involvement is often in the medi- erosive OA with no identifiable cause. • Due to metabolic disorders (e.g., calcium
al joint compartment ( Figure 2 ), but Secondary OA denotes OA caused by pyrrophosphate dihydrate crystals,
involvement of other compartments an underlying condition, including hemochromatosis)
or of the entire joint is also common. those caused by inflammatory dis- • Miscellaneous (e.g., avascular necrosis)
On plain X-ray of an osteoarthrit- eases, trauma, and mechanical factors.
Source: Adapted from Brandt KD.9
ic joint, in addition to joint space nar- In a large series of cases of so-
rowing, there tends to be subchondral called primary osteoarthritis of the
sclerosis or an appearance of whiten- hip, some underlying mechanical Table 2. Classification of OA by cause
ing of the subchondral bone. Osteo- developmental variation could be found
A. Abnormal concentrations of force on
phytes, which reflect a regenerative in most cases to account for the onset normal cartilage
process with formation of fibrocarti- of the disease.10 For instance, the sub- • Cartilage surface irregularities (e.g.,
laginous extensions or hooks at the tle presence of a shallow cup of the intra-articular fractures, meniscal tear)
joint margins, are common. Interest- hip, called acetabular dysplasia, is a • Malalignment of the joint (e.g., leg length
ingly, the presence of osteophytes in common precursor to OA of the hip. disparity, acetabular dysplasia,
congenital hip dislocation)
one compartment, such as the lateral In middle-aged men, femoroacetabu-
• Loss of ligamentous stability (e.g.,
compartment in a patient with medial lar impingement (FAI) is thought to anterior cruciate ligament tear)
compartment OA, is not indicative of be the most common cause of OA of • Loss of protective sensory feedback (e.g.,
disease in that compartment. It is sim- the hip. FAI of the pincer type occurs diabetic neuropathy)
ply indicative of the body’s reparative most often in middle-aged women. On • Other causes (e.g., obesity, occupational)
response to the abnormal stresses and occasion, patients may present with
B. Normal concentrations of force on
presence of disease in the medial com- symptoms of impingement prior to abnormal cartilage
partment. the development of advanced OA. It • Pre-existing arthritis (e.g., rheumatoid
The identification of OA on plain thus appears that the term “primary or arthritis)
X-rays means there is already full idiopathic OA” is probably a mis- • Metabolic abnormalities (e.g., crystal
thickness cartilage loss and even nomer as it applies to the hip or knee, arthropathy)
bone-on-bone contact. These radi- and that if we look hard enough an • Genetic (e.g., generalized osteoarthritis
of hands)
ographic findings occur relatively late underlying structural cause will often
in the course of OA. It would be ideal be apparent. C. Normal concentrations of force on
to be able to identify OA before gross In the 1970s Mitchell and Cruess normal cartilage supported by stiffened
subchondral bone
changes are apparent on radiographs. proposed a more pathogenetic classi-
• Paget disease
Earlier OA detection is important in fication of OA ( Table 2 ). This classi-
identifying disease before the pro- fication system assumes that osteo- D. Normal concentrations of force on
gressive bone-on-bone stage. Joint arthritis can arise from an intrinsic normal cartilage supported by weakened
subchondral bone
ultrasound has been applied in studies problem of the cartilage as encoun-
• Avascular necrosis
to identify OA earlier, but this is more tered after years of chronic inflamma-
a research tool than a routine clinical tory arthritis.11 Thus, OA can occur Source: Adapted from Mitchell NS, Cruess RL.11



is gaining increasing recognition as a
major structural precursor to hip OA.
These are usually asymptomatic before
possible progression to OA and can be
seen on a screening AP pelvis radi-
ograph. Such pre-symptomatic X-
rays, however, are not ordered rou-
Subtle and asymptomatic anatomic tinely.
variations have been associated
Genetic factors
with hip osteoarthritis. The strongest association between
genetic factors and OA applies to gen-
eralized osteoarthritis of the hands.
Evidence for a correlation between
genetics and knee or hip OA is less
conclusive.15,16

Physical activity
Although the health of cartilage and
with (A) normal force on abnormal Gender and the other joint tissues requires regular
cartilage. Alternatively, it can occur estrogen connection joint loading, excessive loading may
with (B) abnormal concentrations of Women are more likely than men to contribute to OA. While some studies
force on normal cartilage. This would have OA, be it generalized OA of the suggest a strong positive relationship
implicate mechanical aberrations such hands or OA of the hips and knees.12 between work-related knee bending
as malalignment, the post-meniscecto- The increase in OA in menopausal exposure and knee OA, others have
my knee, or a cruciate deficient knee. women has led to numerous investi- failed to find a direct relationship
The abnormally formed hip mention- gations into the relationship between between the presence of knee OA
ed above would fall into this category hormonal factors and OA. The results and habitual physical activity or rec-
as well. have been conflicting and inconclu- reational running. 17 A relationship
Mitchell and Cruess’s classifica- sive.13,14 Clearly, other health issues between heavy manual work, farming
tion system also includes situations are of concern when determining in particular, and hip OA was found in
where there is (C) stiffened subchon- whether hormone replacement thera- different studies, but the association is
dral bone, as in the case of the rare py is to be considered in the post- still considered a weak one.18
Paget disease, which does indeed pre- menopausal patient. Although it makes sense that high
dispose to OA of an involved joint. levels of impact and repeated torsion-
Alternatively, they describe situations Congenital/developmental al loading could increase the risk of
where (D) weakened subchondreal abnormalities articular cartilage degeneration, this
bone, as in avascular necrosis, predis- Local factors that affect the shape of is not borne out consistently in stud-
poses to OA. the joint may increase local stress on ies. Still, it would appear prudent to
cartilage and contribute to the devel- suggest that anyone with a known
Risk factors for OA opment of osteoarthritis, especially in underlying predisposition to OA, such
OA is best viewed as the end result of the hip joint. As already mentioned, as abnormal hip or joint anatomy or
an interplay between local and sys- subtle and asymptomatic anatomic excessive body weight, avoid repeti-
temic factors. Such factors are well variations have been associated with tive impact-loading activities such as
outlined in the classification schema hip osteoarthritis. These include ace- jogging.
of mechanical factors proposed by tabular dysplasia or epiphysiolysis,
Mitchell and Cruess. Several local which are common milder variants of Obesity
systemic factors may be operative in congenital hip dislocation and slipped Every step taken in a normal gait places
predisposing patients to OA of the hip capital femoral epiphysis, respective- about three times an individual’s body
or knee. ly.10 Femoralacetabular impingement weight on lower limb joints. Thus it



should not be surprising that obesity tis. An exception to this is the pres- deformity that will challenge accurate
and high body mass index have long ence of intra-articular fractures, that leg length measurement. It is key to
been recognized as potent risk factors is, fractures that extend though the place the patient’s legs in proper align-
for OA, especially medial compart- joint line. The disruption of the carti- ment. There should be an equal dis-
ment OA of the knee in females. lage and subchondral bone with an tance between the medial malleoli
The Framingham Study found that intra-articular fracture does portend a of the ankles, and the feet should be
women who lost about 5 kg had a 50% heightened risk of OA of the involved centred in a neutral position under the
reduction in the risk of developing joint in future decades. Trauma of corresponding hips. The apparent leg
new symptomatic knee OA.19 Weight- the knees leading to internal knee length is measured from the umbilicus
loss interventions have been shown to derangement such as a mensical or to the medial malleolus on each side.
decrease pain and disability in estab- major ligamentous tear will predis- A discrepancy usually signals a scol-
lished knee OA. The Arthritis, Diet, pose to osteoarthritis. In the case of iosis. The true leg length is measured
and Activity Promotion Trial showed the hip, acetabular labral tears, which from the anterior superior iliac spine
that weight loss combined with exer- can only be seen on MRI combined to the medial malleolus, and a discrep-
cise, but not either weight loss or exer- with an arthrogram, will increase the ancy suggests a true variation between
cise alone, was effective in decreasing risk of future OA of the involved hip the two legs. For a true leg length dis-
pain and improving function in obese joint. An acetabular labral tear is often crepancy of more than 1 cm, a shoe lift
elders who already had symptomatic an indication for hip arthroscopy to or built-up orthotic that adjusts for half
knee OA.20 trim the torn fragment. Hip arthros- of the leg length difference is typical-
When patients ask their physicians copy is not often done for diagnostic ly recommended. For a large discrep-
how they can prevent OA of the knees, purposes because MRI is so effective ancy this may not be readily attainable.
weight control is paramount. Unfortu- at picking up lesions. Varus deformities, valgus deform-
nately weight loss is challenging in It is thought that blunt trauma such ities, and cruciate ligament tears are
established OA of the knee due to the as contact with a dashboard in a motor other factors that can predispose to the
limited physical activity possible. vehicle accident can lead to patello- development and progression of knee
The relationship between excess femoral syndrome and chondromala- OA. Detailed discussion of such fac-
weight and hip OA is less clear. The cia patella. However, whether these tors is beyond the scope of this article.
evidence in hip OA is not as compel- pre-OA lesions will progress in future Like the medial compartment and
ling as with knee OA.21,22 decades to full thickness confluent the lateral compartment, the patello-
In addition, there is evidence that cartilage loss signifying OA has not femoral compartment of the knee is
obesity predisposes to osteoarthritis been determined. often afflicted with OA. While injury
in non-weight-bearing joints such as is a common factor in medial and lat-
the joints of the hand. Clearly excess Alignment, including leg length eral compartment OA, malalignment
weight in a biomechanical sense alone Strong evidence suggests that altered is a more common factor in patel-
does not explain this finding. Recent mechanics play a role in OA incidence lafemoral OA. Most cases of chon-
studies have shown that body fat, par- and progression, and recent studies dromalacia patella that result from
ticularly central fat deposits, are bio- are beginning to isolate specific malalignment are nonprogressive, but
chemically active and produce sub- mechanical factors that may be of par- some can progress to OA.24
stances such as leptin and adiponectin.23 ticular importance. Such alignment
It has also been shown that leptin can problems include a leg length discrep- Conclusions
induce the formation of cytokines, ancy of more than 1 cm, which con- OA of the hip and knee is a major
such as interleukin-6, which can have fers an increased risk of OA of the hip health care issue in an ever-aging pop-
a deleterious effect on chondrocytes on the long leg side. All patients ulation. OA of weight-bearing joints
of the cartilage. should be assessed for this. confers major disability and compro-
Leg length measurements include mised quality of life. At this time,
Trauma the apparent and the true leg length. medical treatment of OA is not as
In general, there is a paucity of good To measure leg length, you should sophisticated as the treatment of
documentation to support the con- have the patient lie flat on his or her rheumatoid arthritis. All too often we
tention that blunt trauma to a joint back on the examining table and en- fail with conservative treatment, and
increases the risk of future osteoarthri- sure that there is no hip or knee flexion patients with hip and knee OA progress



to total joint arthroplasty. Advances in al. Correlation between radiographically The risk of osteoarthritis with running and
joint replacement seem to overshad- diagnosed osteophytes and magnetic aging: A 5-year longitudinal study. J
ow advances in more conservative resonance detected cartilage defects in Rheumatol 1993;20:461-468.
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Competing interests CV Mosby; 1974:82. weight and obese older adults with knee
None declared. 11. Mitchell NS, Cruess RL. Classification of osteoarthritis: The Arthritis, Diet, and
degenrative arthritis. Can Med Assoc J Activity Promotion Trial. Arthritis Rheum
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British Columbia Medical Journal, October 2010 issue: Clinical features and pathogenetic mechanisms of osteo - arthritis of the hip and knee