2. Osteoarthritis

Question 1

Osteoarthritis: number of joints affected? inflammatory vs non? timing? distribution?

Answer 1

• could be mono, oligo, or polyarticular
• non-inflammatory
• chronic
• symmetrical

Question 2

osteoarthritis: general features? (progression, cause, age of patients, morning stiffness, appearance of joints?)

Answer 2

slowly progressive, disintegration of cartilage. cause unknown. generally age >50, morning stiffness < 30 min, crepitus, no inflammation, bony enlargement/tenderness can cause secondary damage to surrounding structures

Question 3

primary osteoarthritis - prevalence?

Answer 3

very common. most people get this as they age.

Question 4

secondary osteoarthritis - what is the cause?

Answer 4

degenerative process that was preceded by RA, mechanical or metabolic problem (excessive Fe, ACL tear)

Question 5

OA: what is seen on labs? (ESR, RF titer, fluid aspiration)

Answer 5

ESR < 40

RF Titer < 1:40

non-inflammatory synovial fluid

Question 6

OA: what is seen on imaging?

Answer 6

• osteophytes
• joint space narrowing
• subchondral cysts and sclerosis
• malalignment of joints

Question 7

RA is a disease of what part of the joint?

Answer 7

the synovium. synovium proliferates (almost tumor-like)

Question 8

psoriatic arthritis is a disease of what part of the joint?

Answer 8

synovium and enthesis (tendon)

Question 9

gout, pseudogout, septic arthritis are diseases where what is occuring?

Answer 9

infection and the presence of things in the joint that don’t belong there (urate crystals, bacteria, CPPD- which are another kind of crystals)

Question 10

OA is a disease of what part of the joint?

Answer 10

cartilage. wears away over time

Question 11

Two features of the joint seen in early stage of OA?

Answer 11

• degeneration of cartilage
• reactive new subchondral bone

Question 12

Three features of the joint seen in later stage of disease?

Answer 12

• cartilage particles in joint space
• loss of cartilage -> bone on bone
• bone hypertrophy

Question 13

Articular/hyaline cartilage: what is the main purpose? general qualities? what is it made of?

Answer 13

• shock absorber of diarthroidial joints
• high H20 content, stiffness: like a gel-pack, fluid under pressure
• well-organized arcs of collagen fibers, with proteoglycans in matrix
• chondrocytes interespersed throughout

Question 14

what lies directly beneath articular/hyaline cartilage?

Answer 14

subchondral bone

Question 15

what happens to cartilage in early OA? (grossly)

Answer 15

• increased water content –> soggy
• more pliable
• deformation with loading

Question 16

what happens to cartilage in early OA, at the histological level?

Answer 16

• small tangential clefts on surface
• deeper vertical clefts
• splitting/fibrillation (shagginess)
• chondrocytes clump together

Question 17

Later in OA progression: what happens to cartilage? bone? infiltrates? other structures?

Answer 17

• cartilage -> progressive fibrillation and loss/erosion
• bone: osteophytes and subchondral sclerosis
• some inflammatory infiltrates in synovium
• ligaments -> lax
• weak surrounding muscles
• Bone on bone
  (pic: partial erosion of cartilage, condensation of subchondral bone, osteophyte)

Question 18

general qualities of chondrocytes? (metabolic activity? vascular supply? what do they do? regeneration?)

Answer 18

• only cell type in adult cartilage matrix
• low metabolic activity; no vascular supply
• maintains structure/function of cartilage matrix
• little ability to regenerate
• maintains low turnover rate of ECM proteins

Question 19

OA: what cell type is the main problem?

Answer 19

chondrocytes

Question 20

generally, how do chondrocytes contribute to OA?

Answer 20

normally they are quiescent cells, but in response to stress/injury they will activate –> promote matrix degradation and downreg repair.

Question 21

what are the specific processes by which chondrocytes contribute to OA?

Answer 21

chondrocyte stress leads to proliferation and stress response such as growth factors, cytokines, cartilage-degrading proteinases, other inflammatory mediators -> matrix degradation

Question 22

matrix degradation leads to what?

Answer 22

matrix degradation products feedback and upregulate the chondrocyte stress response -> vicious cycle. may also release anabolic factors -> osteophyte formation

Question 23

which joints does OA most commonly affect?

Answer 23

hands, hips, knees

Question 24

Hand involvement with OA: distribution by gender? which joints most affected?

Answer 24

-Females 4x more likely to have hand involvement than men (more freq found post-menopause). especially basilar thumb joint (first carpometacarpal - CMC).

-Male: wrists more common (possibly occupation-related)

-Both: DIP, PIP

Question 25

general gross appearance of hand joints in OA?

Answer 25

-bony enlargement in DIP and PIP joints. joints look swollen but feel like bone

Question 26

prevalence of OA in various compartments of the knees?

Answer 26

**-75% medial** (so usually yields a VARUS deformity: "knock-knees" - 48% patello-femoral - 25% lateral

Question 27

risk factors in OA?

Answer 27

age, sex, obesity, joint injury, status of ligaments (loose = bad), genetics (genetics impt)

Question 28

women and OA: when is prevalence highest relative to men? possibly due to what? presentation of OA?

Answer 28

-After 50, women \>\> men in terms of OA prevalance -Possibly due to hormonal changes: HRT studies unclear -Women -\> more generalized OA (involvement of hands, spine, knees, hips)

Question 29

general points about obesity and OA?

Answer 29

- being 10 lbs overweight incr forces on knee by 30-60 lbs per step - generally being overweight incr your risk of OA by quite a lot - overweight people have higher rates of hand OA, suggesting **circulating factor** is involved (not just direct pressure on joints)

Question 30

generally, what is the connection between injury and OA?

Answer 30

- injury predisposes to OA - congenital dysplasias (esp hip) - fractures through articular surfaces - inj that leads to joint instability **--Essentially, if you fracture a joint, you are eventually going to get OA in that joint**

Question 31

generally, connection between genetic risk and OA?

Answer 31

in twin studies, genetics account for 50-70% risk in certain joints. BUT no single gene has been identified as responsible

Question 32

OA of the MCPs, especially in a younger person --\> what should I consider?

Answer 32

Hemochromatosis!! Pic: Hand x-ray of pt with hemochromatosis. Note the extensive MCP (esp MCP 2, MCP 3) & wrist disease

Question 33

what are 3 causes of secondary OA? (the three that he starred, from a list of many causes of secondary OA)

Answer 33

- inflammatory joint disease - endocrinopathies - metabolic dz

Question 34

OA: what is the good news/bad news?

Answer 34

- OA is less serious than RA (which is more systemic) - We don't have good treatment for OA

Question 35

Of all the various things we do to treat OA (treating mainly the pain) what has been shown to work?

Answer 35

weight loss, exercise, other non-pharm approaches, joint replacement (one study: diet + exercise improved mobility and pain by 50%)

Question 36

how does exercise help OA?

Answer 36

pain directly correlates with degree of weakness, stronger muscles improve stability and lessen pain. Best is to train muscles of daily activity.

Question 37

Treatment of OA when all else fails?

Answer 37

joint replacement.

Question 38

glucosamine/chondroitin sulfate: benefit to OA patients?

Answer 38

trial says no. measurement = pain score by patient assessment.

Question 39

does arthroscopic surgery to clean out the debris in the knee joint help OA pain?

Answer 39

no. Results were not better than the control, which was a sham surgery!

Question 40

does viscosupplementation (injection of HL Acid into joint) offer any help?

Answer 40

modest effect, helps some patients.

Question 41

does Tanezumab (antibody to inhibit nerve growth factor) help OA?

Answer 41

nope. there was an effect but ultimately the patients on the drug had more knee replacements (incr use of a injured joint that was no longer painful due to meds)

Question 42

in response to mechanical loading of articular cartilage, chondrocytes do all of the following except what?: downregulate collagen proliferate hypertrophy release MMP produce anabolic factors

Answer 42

in response to mechanical loading of articular cartilage, chondrocytes do all of the following except what?: **downregulate collagen** proliferate hypertrophy release MMP produce anabolic factors

Question 43

what compartment of the knee is most commonly affected in OA?

Answer 43

medial

Question 44

average life expectancy of a prosthetic knee joint?

Answer 44

15-20 y, depends on patient

Question 45

If MCPs are predominantly involved, there is ulnar deviation, and the DIPs are spared, should I think RA or OA?

Answer 45

RA

Question 46

if the DIPs are predominantly involved, and the MCPs are somewhat spared, should I think RA or OA?

Answer 46

OA

Question 47

What's going on?

Answer 47

Top pic = normal. Lower pic = Degenerative changes: 1. Diffuse hypercellularity. More chondrocytes, lost a lot of the proteoglycans. Chondrocytes are both proliferating and hypertrophying. 2. Extensive loss of acid mucopoly-saccharide from matrix with diminished red dye fixation.

Question 48

What's going on here?

Answer 48

As cartilage starts to give more under repeated loading, damage starts to occur, basically tearing & cracking Early degenerative changes are now present in this articular cartilage: 1. Small tangential clefts on surface of already altered hyaline cartilage 2. Deeper vertical cleft 3. Splitting process , “fibrillation” 4. Clumping of chondrocytes