Download OSTEOARTHRITIS

OSTEOARTHRITIS
• Osteoarthritis is a degenerative joint disease that
occurs primarily in older individuals and is
characterized by erosion of the articular cartilage,
hypertrophy of bone at the margins (i.e.,
osteophytes), subchondral sclerosis, and a range of
biochemical and morphologic alterations of the
synovial membrane and joint capsule.
• Osteoarthritis may be classified as primary or
secondary according to its cause or major
predisposing factor; both types have in common
altered cartilage physiology.
• Primary osteoarthritis is the most common type and
has no identifiable etiology or predisposing cause.
• Secondary osteoarthritis, although it has an
identifiable underlying cause, is pathologically
indistinguishable from primary osteoarthritis.
• The most common causes of secondary
osteoarthritis are metabolic conditions.
ETIOLOGIC FACTORS IN OSTEOARTHRITIS
• Major factors that affect the degree of risk for
developing osteoarthritis include age, joint location,
obesity, genetic predisposition, joint malalignment,
trauma, and gender.
• AGE
• Age is the risk factor most strongly correlated with
osteoarthritis. Osteoarthritis is the most common
chronic disease that develops in later life. More than
80% of individuals older than 75 years are affected, and
osteoarthritis increases progressively with age at all
joint sites.
• Radiologic changes of osteoarthritis increase as
individuals age, although these changes do not
always correlate with clinical symptoms or disability.
Although an age-related disease, osteoarthritis is not
an inevitable consequence of aging.
JOINT LOCATION
• Although osteoarthritis occurs most commonly in
weight-bearing joints ,age affects joints differentially .A
study comparing tensile fracture stress of cartilage in
the femoral head and in the talus showed that it
decreased progressively with age in the former, but not
in the latter .
• Joint-specific, age-related viability in articular cartilage
may explain why osteoarthritis is more common in hip
and knee joints with increasing age, but occurs rarely in
the ankle.
OBESITY
• Obesity is another important risk factor for
osteoarthritis. Greater body mass index in women
and men has been shown to be associated with an
increased risk of knee, but not hip, osteoarthritis.
• obesity significantly increased the risk of knee
symptoms and radiographic osteophytes.
JOINT MALALIGNMENT AND TRAUMA
• Joint malalignment or trauma may lead to rapid
development of osteoarthritis, or it may initiate a slow
process that results in symptomatic osteoarthritis years
later.
• Probably as a result of progressive reduction in
periarticular blood flow and the resultant decrease in
rate of remodeling at the osteochondral junction, joints
become increasingly congruent with age.
GENDER
• Women are about twice as likely as men to develop
osteoarthritis. Although women have a lower
prevalence of osteoarthritis than men before age 50
years, there is a marked increase in prevalence
among women after age 50, particularly in the knee.
Changes in O.A
• Calcium crystals (e.g., calcium pyrophosphate
dihydrate [CPPD], basic calcium phosphate crystals)
are commonly found in the cartilage of the elderly, and
often crystal arthropathy coexists with osteoarthritis.
• It is unclear, however, whether these crystals are
directly involved in the pathogenesis of osteoarthritis
or are merely a by-product or marker of the disease.
• calcium crystals play a role in causing or worsening
osteoarthritis is supported by clinical and laboratory
studies, but the relationship is complex.
• In osteoarthritis, the expression and production of
proteinases is increased. Native collagen has been shown
to be cleaved by Metaloprotienase(MMP); the resultant
fragments may be susceptible to cleavage by other
enzymes such gelatinase A, gelatinase B, stromelysin 1,
and cathepsin B.
• MMP-13 may be the most important in osteoarthritis
because it preferentially degrades type II collagen .It also
has been shown that expression of MMP-13 greatly
increases in osteoarthritis . Overall, collagenase activity
also markedly increases & it is a major factor in
osteoarthritis progression and cartilage matrix
degradation.
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Radiographic–pathologic correlates in osteoarthritis
Pathological change
Radiographic abnormality
Cartilage fibrillation, erosion
Decrease in interosseous
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distance (localized).
Subchondral new bone formation
Sclerosis.
New cartilage formation and
endochondral ossification
Osteophyte.
Fibrous-walled pseudocysts resulting from
fluid intrusion or myxoid degeneration
Subchondral cysts .
Trabecular compression
Bone collapse .
Fragmentation of osteochondral surface;
cartilage and bone metaphasia in synovium
Osseo('loose')bodies.
Osteophyte formation
• Osteophytes—bony proliferations at the joint
margins and in the floor of cartilage lesions—are
partly responsible for the pain and restriction of
joint movement in osteoarthritis.
• In osteoarthritic joint osteophytes synthesize
cartilage with significant amounts of type I
collagen and nonaggregating proteoglycans.
• Because osteophytes may increase joint surface
available for load bearing, they may contribute to
some cases of regression of the early
osteoarthritis cartilage changes .
osteophytes may occur as a result of penetration of blood
vessels into the basal layers of degenerating cartilage, or
as a result of abnormal healing of stress fractures in the
subchondral trabeculae near the joint margins.
• osteophyte formation begins in the marginal zone,
where synovium merges with periosteum and articular
cartilage
• TGF-β is a known anabolic growth factor that increases
the expression of several types of collagen and
proteoglycans .
• TGF-β induces osteophyte formation, and TGF-β
expression is observed in osteophytes in patients with
osteoarthritis.
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• Bony proliferation may result from venous
congestion. In human hip osteoarthritis,
phlebography has shown the formation of medullary
varices, presumably resulting from changes in the
medullary sinusoids, which may be compressed by
subchondral cysts and thickened subchondral
trabeculae.
• Subchondral cysts in osteoarthritis may be created
by entry of synovial fluid under pressure through
defects in the cartilage or may develop in necrotic
areas of subchondral bone
• The increased venous pressure caused by the cysts
and remodeled trabeculae may account for some of
the pain in osteoarthritis.
• Immobilization and glucocorticoids (but not
bisphosphonates) have been shown to decrease the
size and prevalence of osteophytes in experimental
models of osteoarthritis.
RESPONSE OF CARTILAGE TO MECHANICAL INJURY
• The response of normal articular cartilage to injury typically
results in suboptimal repair; these injuries often can result in
secondary osteoarthritis.
• In contrast to tissues that have the ability to regenerate injured
regions with new cells and extracellular matrices that closely
resemble the original tissue, articular cartilage produces a repair
tissue with neither the original structure nor properties of normal
cartilage.
• Chondrocytes in areas surrounding an injured zone are unable to
migrate, proliferate, repopulate, or regenerate repair tissue with
similar structure, function, and biomechanical properties of
normal hyaline cartilage.
• That articular cartilage lacks regenerative power has a long
history of documentation. The articular cartilage wounds
healed with fibrous tissue, which he believed arose from
chondrocyte intercellular substance.
• So its proposed that cartilage repair is effected by fibrous
tissue resulting from proliferation of cells from bone marrow,
synovial membrane, and occasionally surrounding articular
cartilage. It was later observed that the fibrous tissue
subsequently transforms into fibrocartilage, with occasional
foci of imperfect hyaline cartilage.
• The common findings was that articular cartilage lacks
regenerative potential, and that the regenerative fibrous
tissue and fibrocartilage tissue must have originated from
undifferentiated mesenchymal tissue arising from bone
marrow, synovium, or the superficial layer of articular
cartilage.
• Microdamage to the chondrocytes or extracellular matrix or
both without gross disruption of the articular surface can
be caused by a single severe impact or repetitive blunt
trauma.
• Repetitive loading of cartilage produces a surface loss of
proteoglycans and an increase in chondrocyte metabolic
activity
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Proteoglycans become more easily extractable from the articular
cartilage, with a greater percentage of nonaggregated forms .
• so its observed that cellular, metabolic, and biochemical changes
after repetitive blunt trauma resemble the changes in the early
stages of osteoarthritis—increased hydration, cellular
degeneration or death, disruption of the collagen ultrastructure
resulting in marked variation in the size and arrangements of
fibers, fissuring and ulceration of the articular surface, thickening
of the subchondral bone, and softening of the cartilage with loss
of its compressive and tensile stiffness.
• Trauma induces the release of degradative enzymes and
proinflammatory factors (e.g., nitric oxide, TNF, IL-1)
that frequently cause degradation of the surrounding
matrix.
• Eventually, the material properties of the cartilage are
altered—cartilage matrix thins and subchondral bone
stiffens—which often accelerate the degenerative
process .
• The point at which accumulated microdamage becomes
irreversible is unknown, although it has been shown
that lost proteoglycans and matrix components may be
restored if damage to chondrocytes and the collagen
network is limited, and the repetitive trauma is halted .
ROLE OF INFLAMMATORY MEDIATORS IN
DISEASE PROGRESSION
• Cytokines and Chemokines
• A characteristic feature of established osteoarthritis is the increased
production of proinflammatory cytokines, such as IL-1β and TNF-α, by
articular chondrocytes.
• IL-1β and TNF-α exert comparable catabolic effects on chondrocyte
metabolism, decreasing proteoglycan collagen synthesis and
increasing aggrecan release via the induction of degradative
proteases. IL-1β and TNF-α also induce chondrocytes and synovial cells
to produce other inflammatory mediators, such as IL-8, IL-6, nitric
oxide, and prostaglandin E2.
• The actions of both cytokines are mediated partly by the activation of
the transcription factor nuclear factor κB, which increases further their
own expression and that of other catabolic proteins, such as inducible
nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), creating an
autocatalytic cascade that promotes self-destruction of articular
cartilage .
• IL-1β and TNF-α are synthesized intracellularly as
precursors, converted through proteolytic cleavage to
their mature forms by caspases—membrane-bound IL1β-converting enzyme (ICE) and TNF-α-converting
enzyme (TACE)—and released extracellularly in their
active forms .
• The expression of ICE and TACE has been shown to be
upregulated in osteoarthritis cartilage .
• Inhibitors of ICE and TACE are of interest as future
therapeutic small-molecule antagonists of downstream
IL-1β and TNF-α expression; studies with an ICE
inhibitor are now under way in two murine models.
CLINICAL MANIFESTATIONS
• Pain
• Pain is the first and predominant symptom of osteoarthritis that
sends a patient to the general practitioner. Pain typically is
worsened by activities such as long distance walking for weightbearing joints and is alleviated by rest, in contrast to
inflammatory disorders.
• Pain begins within a few minutes of starting an activity and may
persist for hours after the activity has ceased.
• The pain sometimes can have an onset several hours after
physical activities, especially in young patients. Although
osteoarthritis pain is unusual during the night or at rest
• there are exceptions, including patients with mild
osteoarthritis using joints for several hours especially
during sport, in advanced osteoarthritis with
destructive arthropathy, and in an acute
inflammatory flare of osteoarthritis mimicking
inflammatory arthropathy.
• Associated bursitis also can be a source of pain. Pain
intensity and joint damage on radiographs are poorly
correlated. Finally, there is no agreement as to
whether a decrease in atmospheric pressure or a
change in the weather increases osteoarthritis pain.
• Although pain is the chief complaint its origin is not always
clear. Hyaline cartilage is aneural and this means that
metabolic or structural alteration in this tissue is unlikely to
be directly perceived as painful.
• Several other mechanisms of symptom production have
been suggested ;
• ♦ stimulation of capsular pain fibres and
mechanoreceptors by raised intra-articular pressure due to
synovial hypertrophy, increased fluid production, and
decreased joint compliance;
• ♦ inflammatory mediators stimulating pain fibres in the
synovium and capsule;
• ♦ stimulation of periosteal nerve fibres by intraosseous
hypertension accompanying osteoarthritis;
• ♦ perception of subchondral microfractures;
• ♦ painful periarticular structures such as entheses
and bursae possibly resulting from abnormal
biomechanics and/or muscle weakness;
• ♦ adaptive changes in the spinal cord (central
sensitization, 'wind-up') and brain (disinhibition,
impairment of the Diffuse Noxious Inhibitory
Control system) leading to persistent pain
perception
• Neovasculirisation of cartilage with innervation
by unmyelinated nerve fibers.
• Stiffness and Loss of Movement and Function
• Stiffness also may occur in the morning, after a period of
inactivity, or particularly in the evening. Morning stiffness
generally resolves after less than 10 minutes, in contrast
to the prolonged (usually >30 minutes) stiffness seen in
inflammatory disorders.
• Loss of movement and function reflected in limited range
of motion observed at physical examination is sometimes
the main reason for a visit to the practitioner.
• Patients report limitations in their ability to perform dayto-day activities, such as kneeling for knee osteoarthritis,
or cutting one's toenails for hip osteoarthritis
• Limited joint function is caused by several mechanisms,
including pain, decreased motion related to reduced
joint space, diminished muscle strength, and instability.
Joint proprioceptor sensitivity may be altered; its
relationship to disability is less clear as yet, but is
probably not caused by pain alone .
• Lastly, symptomatic osteoarthritis may be associated
with depression and disturbed sleep, which are
additional contributors to disability.
• Osteoarthritis, wherever it occurs, typically causes pain,
alters function, and leads to a significant deterioration
in the quality of life.
PHYSICAL EXAMINATION
• physical examination should be done to confirm and
characterize joint involvement and to exclude pain and
functional syndromes arising from other causes, especially
periarticluar structures and inflammatory arthritis. A normal
examination does not rule out the diagnosis of osteoarthritis,
however, especially disease of early nature or of modest
severity.
• Bony swelling is easily recognized in superficial joints, such as
the finger joints or knees. A synovial effusion may be seen
during osteoarthritis flares, but also can occur during chronic
phases as a persistent feature.
• Joints are usually tender during active motion testing
and under pressure. Limited passive movement can be
the first and only physical sign of symptomatic
osteoarthritis.
• Bursitis, tendinitis, muscle spasm, and, especially for
the knee, a torn meniscus, can cause the same pain
syndrome and must be sought carefully during
examination .
• Crepitus, an audible or palpable sensation of crunching
or crackling, is commonly felt on passive or active
mobilization of an osteoarthritis joint.
• This sensation is due to the irregularity of the
opposing cartilage surfaces or intra-articular debris.
• Joint deformities reflect advanced disease with joint
destruction involving the cartilage and surrounding
bone and soft tissue, the articular capsule, and the
ligaments.
• the presence of Heberden's or Bouchard's nodes in
the fingers in nodal O.A
Investigation
• 1-Standard radiographs are the most common
investigations, depending on the region involved. Weightbearing radiographs are mandatory for knee and hip
osteoarthritis. A standard radiograph cannot diagnose
early osteoarthritis, however. The radiologic features of
osteoarthritis are .
• Osteophytes at the joint margin, indicating new bone
formation, are the most characteristic feature of
osteoarthritis and usually precede joint space narrowing.
• Subchondral bone sclerosis and joint space narrowing
are classically seen in more advanced osteoarthritis.
Clinical symptoms and radiographic findings are poorly
correlated,
• These are the radiologic features of the most
common form of osteoarthritis—“hypertrophic”
osteoarthritis with bone construction. The other
form, “atrophic” osteoarthritis, is rare, characterized
by an absence of osteophytes and sclerosis; it usually
involves the hip.
• 2-The erythrocyte sedimentation rate and
concentration of the C-reactive protein are usually
within the normal range for age. Low titers of
rheumatoid factors can be found, reflecting the
median age of patients
MANAGEMENT
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Non-pharmacolgic Management of Osteoarthritis
Conventional Options
Patient education
Arthritis self-help courses
Weight loss
Temperature modalities
Exercise
Orthotics
Modified activities of daily living
Unconventional Options
Trans-cutaneous electrical nerve stimulation
Pulsed electromagnetic fields
Static magnets
Acupuncture
Yoga
• Exercise
• Both the dynamic and isometric exercise showed
equivalent improvement in symptoms and physical
functioning .
• Walking can be beneficial, and supervised fitnesswalking regimens can improve function in those with
OA of the knee .
• Home-based exercise interventions also significantly
improve symptoms in those with knee OA.
PHARMACOLOGIC INTERVENTIONS
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Symptom-Relieving Pharmacologic Therapies for Osteoarthritis
Topical
Capsaicin
Topical non-steroidal anti-inflammatory drug (NSAID) preparations
Systemic
Acetaminophen
Nonselective NSAIDs
Cyclooxygenase-2 (COX-2) specific inhibitors
Tramadol
Narcotic analgesics
Intra-articular
Corticosteroids
Hyaluronic acid derivatives
• Glucosamine
• Supplementation with glucosamine sulfate, an intermediate in
mucopolysaccharide synthesis, has been tried both orally and
intramuscularly as therapy for OA.
• Combination products containing both glucosamine and
chondroitin have become quite popular in the United States,
despite a dearth of clinical trial data.
• SURGICAL INTERVENTION
• Surgical interventions in OA usually consist of osteotomies or
joint replacements. Osteotomies can be effective pain-relieving
interventions and can delay the need for joint replacement
surgery in selected patients. These tend to be younger subjects
with OA.
• Other potential rationales for surgical intervention in
OA include removal of loose bodies, stabilization of
joints, redistribution of joint forces (e.g., osteotomy),
and relief of neural impingement (e.g., spinal
stenosis, herniated disk).
• The value of arthroscopic debridement or lavage in
OA has been questioned. A recent randomized,
blinded trial failed to demonstrate significant
symptomatic benefit in OA of the knee