OSTEOARTHRITIS
OSTEOARTHRITIS
OSTEOARTHRITIS
Definition
Osteoarthritis (OA or joint failure) is 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.
Epidemiology
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. The joint sites
most commonly involved are the knees, hips, hands, feet and spine. 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. Older women are at high risk of OA in
all joints, a risk that emerges as women reach their sixth decade. While hormone loss with
menopause may contribute to this risk, there is little understanding of the unique vulnerability of
older women vs. men to OA.
Etiology
Pathophysiology
The OA process is mechanically driven but chemically mediated. 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. This pathology is very
well described, and several classifications and scoring systems are available. The Outerbridge
classification is most commonly used by orthopaedic surgeons.
Grade 1 Softening and swelling of the cartilage
Grade 2 Fragmentation and fissuring of the cartilage in an area less than ½ inch in
diameter
Grade 3 Fragmentation and fissuring of the cartilage in an area more than ½ inch in
diameter
Grade 4 Exposure of underlying bone.
In addition to being a primary target tissue for disease, cartilage also functions as a joint
protector. A thin rim of tissue at the ends of two opposing bones, cartilage is lubricated by
synovial fluid to provide an almost frictionless surface across which these two bones move.
Since the earliest changes of OA may occur in cartilage and abnormalities there can accelerate
disease development, understanding the structure and physiology of cartilage is critical to an
appreciation of disease pathogenesis. The two major macromolecules in cartilage are type 2
collagen, which provides cartilage its tensile strength, and aggrecan, a proteoglycan
macromolecule linked with hyaluronic acid, which consists of highly negatively charged
glycosaminoglycans. In normal cartilage, type 2 collagen is woven tightly, constraining the
aggrecan molecules in the interstices between collagen strands, forcing these highly negatively
charged molecules into close proximity with one another. The aggrecan molecule, through
electrostatic repulsion of its negative charges, gives cartilage its compressive stiffness.
Chondrocytes, the cells within this avascular tissue, synthesize all elements of the matrix. In
addition, they produce enzymes that break down the matrix and cytokines and growth factors,
which in turn provide autocrine/paracrine feedback that modulates synthesis of matrix molecules
(Fig. 19-3). Cartilage matrix synthesis and catabolism are in a dynamic equilibrium influenced
by the cytokine and growth factor environment. Mechanical and osmotic stress on chondrocytes
induces these cells to alter gene expression and increase production of inflammatory cytokines
and matrix-degrading enzymes. While chondrocytes synthesize numerous enzymes, especially
matrix metalloproteinases (MMP), only a few of these enzymes are critical in regulating cartilage
breakdown. Type 2 cartilage is degraded primarily by MMP-13 (collagenase 3), with other
collagenases playing a minor role. Aggrecan degradation is a consequence, in part, of activation
of two aggrecanases (ADAMTS-4 and ADAMTS-5) and perhaps of MMPs. Both collagenase
and aggrecanases act primarily in the territorial matrix surrounding chondrocytes; however, as
the osteoarthritic process develops, their activities and effects spread throughout the matrix,
especially in the superficial layers of cartilage.
The synovium and chondrocytes synthesize numerous growth factors and cytokines. Chief
among them is interleukin (IL) 1, which exerts transcriptional effects on chondrocytes,
stimulating production of proteinases and suppressing cartilage matrix synthesis. In animal
models of OA, IL-1 blockade prevents cartilage loss. Tumor necrosis factor (TNF) α may play a
similar role to that of
IL-1. These cytokines also induce chondrocytes to synthesize prostaglandin E2, nitric oxide, and
bone morphogenic protein 2 (BMP-2), which together have complex effects on matrix synthesis
and degradation. Nitric oxide inhibits aggrecan synthesis and enhances proteinase activity,
whereas BMP-2 stimulates anabolic activity. At early stages in the matrix response to injury and
in the healthy response to loading, the net effect of cytokine stimulation may be matrix synthesis
but, ultimately, excess IL-1 triggers matrix degradation.
After an injury to cartilage, chondrocytes undergo mitosis and clustering. While the metabolic
activity of these chondrocyte clusters is high, the net effect of this activity is to promote
proteoglycan depletion in the matrix surrounding the chondrocytes. This is because the catabolic
is greater than the synthetic activity. As disease develops, collagen matrix becomes damaged, the
negative charges of proteoglycans get exposed, and cartilage swells from ionic attraction to water
molecules. Because in damaged cartilage proteoglycans are no longer forced into close
proximity, cartilage does not bounce back after loading as it did when healthy, and cartilage
becomes vulnerable to further injury. Chondrocytes at the basal level of cartilage undergo
apoptosis.
With loss of cartilage come alterations in subchondral bone. Stimulated by growth factors and
cytokines, osteoclasts and osteoblasts in the subchondral bony plate, just underneath cartilage,
become activated. Bone formation produces a thickening and stiffness of the subchondral plate
that occurs even before cartilage ulcerates. Trauma to bone during joint loading may be the
primary factor driving this bone response, with healing from injury (including microcracks)
producing stiffness.
At the margin of the joint, near areas of cartilage loss, osteophytes form. These start as
outgrowths of new cartilage and, with neurovascular invasion from the bone, this cartilage
ossifies. Osteophytes are an important radiographic hallmark of OA. In malaligned joints,
osteophytes grow larger on the side of the joint subject to most loading stress (e.g., in varus
knees, osteophytes grow larger on the medial side). The synovium produces lubricating fluids
that minimize shear stress during motion. In healthy joints, the synovium consists of a single
discontinuous layer filled with fat and containing two types of cells, macrophages and
fibroblasts, but in OA, it can sometimes become edematous and inflamed. There is a migration of
macrophages from the periphery into the tissue, and cells lining the synovium proliferate.
Enzymes secreted by the synovium digest cartilage matrix that has been sheared from the surface
of the cartilage. Additional pathologic changes occur in the capsule, which stretches, becomes
edematous, and can become fibrotic.
Clinical Manifestation
Joint pain from OA is activity-related. Pain comes on either during or just after joint use and then
gradually resolves. Examples include knee or hip pain with going up or down stairs, pain in
weight-bearing joints when walking, and, for hand OA, pain when cooking. Early in disease,
pain is episodic, triggered often by a day or two of overactive use of a diseased joint, such as a
person with knee OA taking a long run and noticing a few days of pain thereafter. As disease
progresses, the pain becomes continuous and even begins to be bothersome at night. Stiffness of
the affected joint may be prominent, but morning stiffness is usually brief (<30 min). In knees,
buckling may occur, in part, due to weakness of muscles crossing the joint. Mechanical
symptoms, such as buckling, catching, or locking, could also signify internal derangement, such
as meniscal tears, and need to be evaluated.
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.
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. 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 movement
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. Pain is felt globally over the knee and the
proximal tibia. 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. 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 inflammation 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.
Imaging
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
Laboratory testing
No blood tests are routinely indicated for workup of patients with OA unless symptoms and
signs suggest inflammatory arthritis. Examination of the synovial fluid is often more helpful
diagnostically than an x-ray. If the synovial fluid white count is >1000 per μL, inflammatory
arthritis or gout or pseudogout are likely, the latter two being also identified by the presence of
crystals.
Treatment
The goals of the treatment of OA are to alleviate pain and minimize loss of physical function. To
the extent that pain and loss of function are consequences of inflammation, of weakness across
the joint, and of laxity and instability, the treatment of OA involves addressing each of these
impairments. Comprehensive therapy consists of a multimodality approach including
nonpharmacologic and pharmacologic elements. Patients with mild and intermittent symptoms
may need only reassurance or nonpharmacologic treatments. Patients with ongoing, disabling
pain are likely to need both nonpharmaco- and pharmacotherapy.
Nonpharmacotherapy
Since OA is a mechanically driven disease, the mainstay of treatment involves altering loading
across the painful joint and improving the function of joint protectors, so they can better
distribute load across the joint. Ways of lessening focal load across the joint include
(1) avoiding activities that overload the joint, as evidenced by their causing pain;
(2) improving the strength and conditioning of muscles that bridge the joint, so as to optimize
their
function; and
(3) unloading the joint, either by redistributing load within the joint with a brace or a splint or by
unloading the joint during weight bearing with a cane or a crutch.
The simplest effective treatment for many patients is to avoid activities that precipitate pain. For
example, for the middle-aged patient whose long-distance running brings on symptoms of knee
OA, a less demanding form of weight-bearing activity may alleviate all symptoms. Each pound
of weight increases the loading across the knee three- to sixfold. Weight loss may have a
commensurate multiplier effect, unloading both knees and hips. Thus, weight loss, especially if
substantial, may lessen symptoms of knee and hip OA. In hand joints affected by OA, splinting,
by limiting motion, often minimizes pain for patients with involvement either in the base of the
thumb or in the DIP or proximal IP joints. With an appropriate splint, function can often be
preserved. Weight-bearing joints such as knees and hips can be unloaded by using a cane in the
hand opposite to the affected joint for partial weight bearing.
Pharmacotherapy
While nonpharmacologic approaches to therapy constitute its mainstay, pharmacotherapy serves
an important adjunctive role in OA treatment. Available drugs are administered using oral,
topical, and intraarticular routes. Acetaminophen (paracetamol) is the initial analgesic of choice
for patients with OA in knee, hip, or hands. For some patients, it is adequate to control
symptoms, in which case more toxic drugs such as NSAIDs can be avoided. Doses up to 1 g 3
times daily can be used to a maximum of 3000 mg per day. NSAIDs are the most popular drugs
to treat osteoarthritic
pain. They can be administered either topically or orally. In clinical trials, oral NSAIDs produce
∼30% greater improvement in pain than high-dose acetaminophen. Occasional patients treated
with NSAIDs experience dramatic pain relief, whereas others experience little improvement.
Initially, NSAIDs should be administered topically or taken orally on an “as needed” basis
because side effects are less frequent with low intermittent doses, which may be highly
efficacious. If occasional medication use is insufficiently effective, then daily treatment may be
indicated, with an anti-inflammatory dose selected (Table 19-1). Patients should be reminded to
take low-dose aspirin and ibuprofen at different times to eliminate a drug interaction.
NSAIDs taken orally have substantial and frequent side effects, the most common of which is
upper gastrointestinal toxicity, including dyspepsia, nausea, bloating, gastrointestinal bleeding,
and ulcer disease. To minimize the risk of nonsteroidal related GI side effects, patients should
not take two NSAIDs, and should take medications after food; if risk is high, patients should take
a gastroprotective agent, such as a proton pump inhibitor.
Intraarticular Injections: Glucocorticoids and Hyaluronic Acid
Since synovial inflammation is likely to be a major cause of pain in patients with OA, local anti-
inflammatory treatments administered intraarticularly may be effective in ameliorating pain, at
least temporarily. Glucocorticoid injections provide such efficacy, but work better than placebo
injections for only 1 or 2 weeks. Glucocorticoid injections are useful to get patients over acute
flares of pain and may be especially indicated if the patient has coexistent OA and crystal
deposition disease, especially from calcium pyrophosphate dihydrate crystals. Hyaluronic acid
injections can be given for treatment of symptoms in knee and hip OA, but there is controversy
as to whether they have efficacy vs. placebo
Surgery
For knee OA, several operations are available. Among the most popular surgeries, at least
in the United States, is arthroscopic debridement and lavage.
Differensial Diagnosis
RA
GOUT