OA

Question 1

What joints does OA most commonly affect?

Answer 1

cervical and lumbosacral spine, hip, knee and first MTP. DIP and PIP are also affected - Heberden’s nodes (DIP) and Bouchard’s nodes (PIP)

Question 2

what are the structural pathological features of OA?

Answer 2

loss of hyaline articular cartilage, osteophytes, subchondral sclerosis and bone cuts , mild synovitis

Question 3

What age is most affected by OA?

Answer 3

uncommon 60

at age 65, 80% have radiographic OA changes but only 25% are symptomatic

Question 4

Name and describe the two major components of cartilage.

Answer 4

1. Type 2 collagen
   - provides cartilage with its tensile strength
   - in normal cartilage is tightly woven constraining aggrecan molecules
2. Aggrecan
   - proteoglycan macromolecule linked with hyaluronic acid
   - gives cartilage its compressive stiffness

Question 5

What are the main clinical features of OA?

Answer 5

Joint pain worse during or just after joint use with improves with ongoing use
Morning stiffness
Nocturnal pain occurs with advanced disease - would expect significant x-ray changes or seek alternative Dx

Question 6

What are the features of synovial fluid examination in OA

Answer 6

WCC

Question 7

Name some non-pharmacotherapy treatments for OA.

Answer 7

altering loading across the joint:

• avoid activities that overload the joint
• strengthen muscles that support the joint
• braces, walking stick to offload the joint
• weight loss - force 3-6 times throughout the joint when walking

Question 8

Describe the role of a chondrocyte

Answer 8

synthesise all elements of the cartilage matrix

• synthesis and catabolism are under the influence of cytokines and growth factors
• mechanical and osmostic stress on chondrocytes induce them to alter gene expression and increase production of inflammatory cytokines and matrix degrading enzymes

Question 9

what are the characteristic changes in cartilage in OA?

Answer 9

depletion of aggrecan
unfurling of the tightly woven collagen matrix
loss of type 2 collagen
- cartilage loses its compressive stiffness

Question 10

What role do chondrocytes have in cartilage turnover?

Answer 10

• produce matrix molecules - aggrecan, collagen type 2

- produce enzymes responsible for degradation of collagen matrix - matrix metalloproteinases (MMP), ADAMTS-5

Question 11

List the cytokines involved in the bony remodelling of OA

Answer 11

Vascular endothelial growth factor (VEGF)
Interleukin (IL)
Transforming growth factor (TGF)
Tumour Necrosis Factor (TNF)

(exert transcriptional effects on chondrocytes stimulating the production of proteinases and suppressing cartilage matrix synthesis
induce chondrocytes to produce prostaglandin E2 and NO which have complex effects on cartilage synthesis and degradation

Question 12

List some risk factors for OA

Answer 12

Age
Female > male
Genetics
Ethnicity 
- hip OA rare in China but knee OA just as common if not more so than whites
Nutrional factors
Previous trauma/joint damage
Malalignment
Proprioceptive deficiencies - e.g. Charcot foot
Obesity

Question 13

Discuss the genetics involved in OA

Answer 13

30% knee OA heritable
50% hand and hip OA heritable
* Polymorphism within the growth differentiation factor 5 gene - diminishes the quantity of GCDF5
- main influence of GDF5 is on joint shape
* Point mutations in COL2A1 gene which encodes for type 2 collagen

Question 14

What are the pharmacological management options for OA?

Answer 14

Paracetamol
NSAID - PRN initially
Intra-articular injections
- temporarily reduce synovial inflammation
- useful in acute flares

Question 15

What’s the deal with glucosamine and chondroitin?

Answer 15

compared with placebo there is no improvement in pain or joint space narrowing in meta-analysis
- not recommended

Question 16

What is the problem with COX-2 inhibitors?

Answer 16

Increased cardiovascular events

In 2004 Vioxx taken off the market due to significantly increased risk of acute MI compared to Naproxen

• Celcoxib OK in low doses
• Naproxen is the only NSAID that appears to be safe from a cardiovascular perspective (but GI toxicity remains)

Question 17

What are the indications for surgery?

Answer 17

pain despite medical treatment
limitations of physical function that compromise QOL
- highly efficacious surgery that improves pain and function although rates of success are higher for hip than knee replacement
- should be performed before disease is so bad that muscle wasting etc has occurred