what are the risk factors of osteoarthritis?
- age
- 25% >50yes have knee OA - women
- obesity
- smoking
- hypermobility
- osteoporosis
what is OA?
what does articular cartilage do? where is it?
absorb load of the joint
- knee joint - end of femur and tibia
- hip joint - fem
what is the structure of articular cartilage?
made up of chrondrocytes
produce proteins that form the extracellular matrix
what are proteins that form the extracellular matrix?
- Network of Type II Collagen fibres
- Proteoglycans containing glycosaminoglycan (GAG) side- chains
* “Bottle-brush” appearance
* Trap water, which provides cartilage with its load absorbing properties - Non-collagenous proteins including fibronectin
how does articular cartilage absorb load?
When load is applied to the joint cartilage compresses H2O
In turn repulsive forces from proteoglycans within the extracellular matrix balance the load applied
On removing load, proteoglycans rehydrate restoring shape of cartilage
what is chondrocyte hypertrophy?
chondrocyte proliferate and undergo hypertrophy :
1. induce transcriptional factors = increase hypertrophy
2. reduce matrix synthesis - collagen and aggrecan proteoglycan
3. increase matrix proteases
how does cartilage degeneration occur in OA?
catabolic processes:
1. matrix metalloproteases (MMPs) - degrade type 2 collagen
2. aggrecanases - degrade aggrecan proteoglycans
how is the subchondral bone describes in OA?
sclerotic
how is bone described in OA?
undermineralised
abnormal type 1 collage - increase expression of alpha-1 collagen = kink structure = brittle bone
what does OA synovitis cause?
inappropriate activity of fibroblast cells = increase joint damage and joint pain
whats first line for OA treatment?
- topical/oral NSAID’s
- aspirin/ibuprofen (long-term GI issues)
OR
selective COX-2 inhibitors for long term use - less GI issues but INC CV risk
- celecoxib/meloxicam
- GC intra-articular injection used in knee OA
- known to also accelerate cartilage damage
how do GC accelerate cartilage damage?
- increase RANKL = decrease OPG secretion from osteoblasts
- chronic increase of PTH and reduction in BMP2 = decreases osteoblasts proliferation
- increase apoptosis of osteocytes = decrease load sensing and initiation of bone remodelling
why is obesity a risk factor for OA?
- traumatic loading can induce cartilage damage= increasing cartilage fragmentation
- increased adipose tissue secrete cytokines (pr-inflammatory)
what does a high WHR suggest?
metabolic syndrome related effect
