Wk.7 L4 - Osteoarthritis Flashcards
(11 cards)
LO
- Outline the societal and personal burden of osteoarthritis
- Describe how mechanobiology is important for normal synovial joint function
- Recall the basic pathophysiology of osteoarthritis
- Explain the concept of disease phenotypes
Osteoarthritis (OA)
- > 500 million people worldwide
- 62% female
- Over 50% are < 65 (“working age”)
- 25% cant do daily activities
- Huge burden $3.75b AUD
OA discovery research
NO CURE for OA
- NO registered disease modifying therapies
- POOR long-term pain/disability management
To develop effective treatments, we need improved understanding of the pathophysiology of the disease and symptomology
Synovial Joints: normal morphology and function
joint functions as an organ:
- different tissues work together for joint to function
- biological system
[slides]
Synovial Joints: mechano-biology
Integration of mechanical and biological functions
Bone:
- diaphysis to metaphysis to subchondral plate
- absorb & translate load
- remodelling
Cartilage:
- calcified (deep) and non-calcified layers
- different morphology, biochemistry, metabolism and function
- Compression resistant
Synovium & synovial fluid:
- filtration barrier
- Lubrication
- Source of cartilage nutrition
Joint capsule & ligaments:
- constrain & regulate ROM
- intra-synovial fat pads – lubrication, immune function
Meniscus:
- inner versus outer compositional differences
- load translation & dissipation, lubrication
Nerves:
- autonomic and sensory
- proprioception & nociception
- Feedback
Muscle:
- motor function
- Feedback
OA - a disease of the “joint organ”
Pathology and abnormailty in all of the joint tissues:
Bone:
- increased formation, turnover and vascularisation
Cartilage:
- collagen (II) breakdown
- Loss of mechanical function
Synovial fluid, synovium & joint capsule:
- Loss of SF, HA & lubricin
- Inflammation and casule fibrosis
Meniscus & Ligaments:
- altered composition, tears
- Loss of biomechanical function
Nerves:
- increased number and sensitization
OA - NOT simply “wear & tear”
Active disease process of the cells in the different joint tissues
Can be initiated in any of the joint tissues
OA - inter-related tissue pathologies
Defining the pathways and how they change with time will identify targets to modify OA initiation and progression
OA - pre-clinical research
> 450 genes/molecular-targets significant, BUT:
- ~30% show beneficial effect on one OA tissue
pathology but not another
- ~30% have inconsistent and even opposite effect in different disease models
OA - phenotypes & endotypes
Is a collection of diseases with observable phenotypes and endotypes
There wont be a single treatment for OA
OA - defining disease complexity
offers hope for effective therapy
May need:
- multi-tissue approach
- pathology & pain therapies
- phenotype-targeted therapies
- biomarkers to identify endotype
