Osteoarthritis

Question 1

What is osteoarthritis?

Answer 1

joint failure, a disease in which all structures of joint have undergone pathologic change, often in concert

hyaline articular cartilage loss, present in focal and, initially nonuniform manner

there are numerous pathways that lead to joint failure, but initial step is often joint injury in the setting of failure of protective mechanisms

Question 2

pathological findings in osteoarthritis

Answer 2

main one is hyaline articular cartilage loss

thickening and sclerosis of subchondral bony plate, by outgrowth of osteophyes at joint margin

stretching of articular capsule

mild synovitis in many affected joints

weakness of muscles bridging joint

Question 3

Why is the societal impact of osteoarthritis so large?

Answer 3

most common form of arthritis in humans

does not lead to disability ineveryone but is a common painful condition that increases with age

inadequacy of current treatment allows it to be the leading cause of chronic disability

risk of disability attributable to knee osteoarthritis in elderly

Question 4

systemic risk factors for incident OA

Answer 4

age (all joint sites)

gender (all sites)

genetic factors (many sites, especially hand)

excess body weight (especially knee)

certain occupations

elite athletic activity

Question 5

local risk factors for incident OA

Answer 5

major injury (all, even atypical sites)

meniscectomy (knee)

developmental abnormalities (especially hip)

varus alignment (knee)

meniscal tear, meniscal extrusion (knee)

Question 6

What age-related changes contribute to development of OA?

Answer 6

decline in neuromuscular joint protective mechanisms (muscle function, proprioception, soft tissues sthat stabilize joints)

decline in biomechanical properties of cartilage matrix

reduced ability of joint to rebound from injury

reduced regenerative potential of joint tissue

Question 7

How does excess body weight affect risk of getting OA?

Answer 7

increases risk of incident and progressive knee OA

weight in young adulthood/middle age predicts knee OA risk later in life

in overweight persons, weight reduction reduces risk of incident knee OA

increases risk of hip OA (less than for knee)

Question 8

What are the structures that protect the joints?

Answer 8

joint capsule and ligaments - soft tissue restraint to excessive motion, mechanireceptors via sensory afferent nerves and spinal cord provide feedback for muscle activity

muscles and tendons - activity helps to decelerate joint before impact and to distribute load

synovial fluid - helps to reduce friction between articulating cartilage surfaces

failure of these joint protectors increases risk of joint injury and OA

Question 9

What is the process of repair in response to join insult in OA?

Answer 9

destruction and repair of joints

attempt by all joint components to produce new tissue:

• new bone (osteophytes)
• synovial hyperplasia
• capsular thickening
• initial increase in chondrocyte number and activity

Question 10

What is the natural history of OA?

Answer 10

site of initial insult may be any tissue of the joint

compensated OA - joint remodeling keeps pace with tissue loss

decompensated OA - severity/chronicity of insult outweighs repair process

natural history of one joint includes compensated and decompensated phases

not all joints with OA experience disease progression

Question 11

What happens in compensated OA?

Answer 11

increased chondrocyte activity

new bone formation

capsular thickening sustains stability

mechanical forces redistributed across the compromised joint

Question 12

What happens in decompensated OA?

Answer 12

disease progression

symptoms start occurring

disability results

Question 13

What component of carilage provides most of its ability to sustain a load?

Answer 13

hydrostatic pressure in the interstitial water

water is absorbed because of the hydrophilic nature of the aggrecans

Question 14

Whay happens to cartilage in OA?

Answer 14

gradual depletion of aggrecan

unfurling of tightly woven collagen matrix

loss of type II collagen

cartilage has greater water content due to destruction of collagen network and proteoglycan loss - impairs ability of cartilage to sustain load

without is compressive stiffness, cartilage becomes more vulnerable

Question 15

What are the factors involved in balance of synthesis and catabolism in articular cartilage?

Answer 15

self-repair proteins (PDGF, IGF-1, TGF-beta)

cytokiens (IL1, TNFalpha)

lipid mediators (prostaglandins)

free radicals (NO)

matrix degradation products

synovial cells

Question 16

What is the role of synovial cells in the balance of synthesis and catabolism in articular cartilage?

Answer 16

phagocytize cartilage fragments released into joint

synovial inflammation

synovial cells release matrix metalloproteinases and cytokines which further alter extracellular matrix and activate chondrocytes

Question 17

What is the role of matrix metalloproteinases in cartilage degradation?

Answer 17

main proteinases involed in cartilage destruction of OA

made by chondrocytes and synoviocytes under influence of cytokines

activities controlled by TIMPs (tissue inhibitors of metalloproteinases)

major proteinases involved in tissue destruction - collagenase-3 (MMP13) and aggrecanase-1 (ADAMSTS4)

these enzymes are a potential target for drug development to try to modify disease course

Question 18

What is the pathology of OA?

Answer 18

cartilage - initial surface fibrillation and irregularity, then full thickness defect (extending down to bone), then larger area of cartilage damaged and/or lost, leaving bare bone

bone - thickening and stiffness of subchondral plate, osteophytes form at joint margins

synovium - can become edematous and inflamed

capsule - edema, and later fibrosis

Question 19

OA phase 1

Answer 19

edema of extracellular matrix

microcracks appear on cartilage surface

focal loss of chondrocytes, alternating with areas of chondrocyte proliferation

Question 20

OA phase 2

Answer 20

microcracks deepen

vertical clefts form in cartilage

clusters of chondrocytes appear around these clefts and at surface

Question 21

OA phase 3

Answer 21

fissures cause cartilage fragments to break off (osteocartilaginous loose bodies

subchondral bone uncovered

subchondral cysts

mild synovial inflammation (more focal and milder than RA)

subchondral bone sclerosis

Question 22

What are the common sites affected by primary OA?

Answer 22

hands - distal interphalangial (DIP), proximal interphalangeal (PIP), first metacarpal (CMC)

cervical and lumbar spine

feet - especially 1st metarsophalangeal (MTP)

knees - medial or lateral compartment (not both), patellofemoral involvement may accompany tibiofemoral or be present alone

hips - superolateral or inferomedial narrowing

Question 23

What are the joints commonly affected in secondary OA?

Answer 23

MCP, wrist, elbow, shoulder, ankle

often premature onset

Question 24

generalized OA

Answer 24

defined as OA in hands and at least one large joint:

• familial predisposition
• more common in women, onset middle age
• multiple Heberden’s nodes
• polyarticular finger interphalangeal joint OA
• symptoms persist for years, but settle down
• later predisposition to OA at other common OA sites especially knee and medial//patellofemoral

Question 25

What are the patterns of joint involvement in OA?

Answer 25

mono-, oligo-, or poly-articular

Question 26

What are the common symptoms of OA?

Answer 26

pain morning stiffness stiffness after inactivity swelling knee - pain/difficult with stairs, sit-to-stand, feeling that knee may give way hip - pain in growin or deep posterolateral, pain/difficult with getting in/out of car, putting on shoes and socks spine - pain in region of involvement, radicular symptoms if nerve roots compressed by osteophytes

Question 27

What are the characteristics of pain associated with OA?

Answer 27

aching pain early OA - increases with joint use, relieved by rest, relieved by simple analgesics advanced OA - pain at rest as well as with use, night pain, not relieved easily, sleep interference impacts well-being and worsens pain experience pain/structure change closest relationship at hip, weakest at hand and spinal apophyseal joints

Question 28

What are the physical exam findings indicating OA?

Answer 28

bony enlargement limitation of motion - limited flexion, inability to achieve full extension peri-articular muscle weakness crepitus malalignment mild inflammation, warmth, effusion (if moderate or severe, consider joint infection or acute crystal process)

Question 29

synovitis as a warning sign of OA

Answer 29

acute or subacute - flares are common in OA and may show mild joint inflammation more marked synovitis warrants urgent investigation for another cause (crystal, septic arthritis - damaged joints are predisposed, coexisting CPPD and septic arthritis)

Question 30

general clinical characteristics of OA

Answer 30

onset tends to be gradual usually only one/few joints problematic at any given time evolution of symptoms and structure change tends to be slow strong age association (men 40s and older, women peri-menopause and older)

Question 31

laboratory findings in OA

Answer 31

blood and urine tests have no role synovial fluid analysis reveals non-inflammatory fluid characteristics: - low turbidity - low white blood cell count (\<2000) - may show CPPD (calcium pyrophosphate dihydrate) crystals

Question 32

radiographic findings in OA

Answer 32

focal joint space narrowing marginal and central osteophytes subchondral sclerosis and cysts osteochondral bodies bony attrition

Question 33

role of x-ray in OA

Answer 33

help confirm diagnosis (and rule out other suspected conditions) assess OA severity, which helps develop pland and treat as well as understand prognosis and expected course

Question 34

role of MRI in OA

Answer 34

MRI plays a large role in research, but a small role in OA patient care

Question 35

When is MRI useful for OA?

Answer 35

if the patient is considering referral for arthroscopy patient in whom avascular necrosis is a possibility patient with unusual features of pattern or course

Question 36

causes of secondary OA

Answer 36

any other arthritis injury developmental abnormalities (acetabular dysplasi) osteonecrosis CPPD, apatite crystal deposition disease Paget's disease hemochromatosis onchronosis hyperparathyroidism Wilson's disease acromegaly

Question 37

What are the outcomes of OA?

Answer 37

disease progression - structural changes at the joint level symptoms - pain and stiffness physical function decline - decline in performance of discrete actions disability - limitation in performance of socially defined tasks expected of an individual within a typical environment

Question 38

What is the prognosis for individuals with OA?

Answer 38

prognosis is variable from one person to the next and from one joint to the next some have disease progression but not functional decline or disability others have functional decline or disability but no disease progression worsening is not inevitable

Question 39

factors associated with disease progression in knee OA

Answer 39

excess body weight varus alignment valgus alignment meniscal damage

Question 40

factors associated with functional decline in knee OA

Answer 40

pain severity excess body weight inactivity muscle weakness joint laxity low self-efficacy depression/anxiety poor social support other medical conditions

Question 41

treatment goals in OA

Answer 41

relieve symptoms maintain or improve function limit disability avoid drug toxicity modify disease course - no drug available as yet that achieves this goal

Question 42

non-pharmacologic treatment for OA

Answer 42

**mild or intermittent symptoms** - may only need reassurance or non-pharm treatment **patient education** - self management and social support **physical and occupational therapy:** - exercise to preserve range of motion, strength, aerobic capacity - assistive devices improve ambulation and ADLs **weight loss (if overweight)**

Question 43

What are the available systemic pharmacologic treatments for OA?

Answer 43

non-narcotic analgesic (ex. ecetaminophen) anti-inflammatory (NSAIDS and selective cyclooxygenase-2 inhibitors) narcotic analgesics (for advanced OA)

Question 44

What are the local pharmacologic treatments for OA?

Answer 44

intra-articular corticosteroid treatment hyaluronic acid - **no evidence**

Question 45

When should NSAIDs be used for OA? What types are there?

Answer 45

consider first with severe pain and signs of inflammation 2 forms - COX-1 expresse din many tissues and COX-2 in normal tissue in response to physiological stress selected COX-2 inhibitors have improved benefit-to-GI risk rario, but offer little advantage in terms of other toxicities - may have greater CV risk

Question 46

glucosamine and chondroitin for OA

Answer 46

efficacy is not certain recent trials suggest borderline to no disease modifying effect

Question 47

What are some future treatments for OA?

Answer 47

tissue engineering - chondrogenic precursor cell populations or chondrocytes combined with scaffold and growth factors

Question 48

surgical therapy for OA

Answer 48

in advanced OA, can do total joint replacement in mild/moderate OA without response to conservative therapy, the role of surgical options is much less clear arthroscopy may play a role if mechanical symptoms are present, but improvements in outcome are uncertain