Cartilage+OA Flashcards
What fraction of people above 45yrs seek treatment for OA?
1/3
-81% of these have constant pain or functional limitations
-7.5 million working days lost per year in UK
-OA pain is the commonest reason for joint replacement
-USA: predicted 0.5M hip replacements each year by 2030
What is the commonest reason for joint replacement?
OA
What is shown in this arthroscopy?
A chondral defect
What components make up the cartilage ECM and what are 2 of their functions?
Aggrecan(type of proteoglycan)-Resist compression
T2 collagens-High tensile strength
Water
Outline the function of the chondrocyte
<5% tissue
Producer and degrader of the cartilage matrix
Highly metabolically active
Exist in relative hypoxia
Interactions with matrix: growth factors, mechano-transduction
No cell division after adolescence
Give the 4 layers of hyaline cartilage including the location of the tide mark
Superficial layer
Transitional/Intermediate
Deep/Radial
(Tide mark)
Calcified
——-Bone
What type of enzyme breaks down collagen?
Collagenases-A type of metalloproteinase
Which metalloproteinase are useful for breaking down collagen?
MMPs-3,11,18
What type of molecule is MMP-3?
A stromelysin
Outline the structure of aggrecan
Sugar chains off of a protein backbone, attached to hyaluronan, contains 3 major domains
-Branches of keratin sulphate and chondroitin sulphate
Where can aggrecan be cleaved and by what?
Matrix metalloproteinases between amino acids 341-342
Aggrecanases between amino acids 373-374
What are the intrinsic anabolic/anti-catabolic factors for articular cartilage?
TIMPs (Tissue Inhibitor of Metalloproteinases) 1-4
Growth factors e.g. fibroblast growth factor (FGF-2), Insulin-like growth factor (IGF), Transforming growth factor (TGF)-β, activin A
What are the extrinsic anabolic/anti-catabolic factors for articular cartilage?
Hormones e.g. testosterone, estrogen
Some drugs e.g. FGF-18
Simply, why does cartilage matrix loss occur?
Excessive degradation compared to repair
What part of your knee supports most of the weight?
The medial compartment
What occurs if your joints are absent of mechanical load?
You can’t maintain cartilage thickness and turnover, leading to cartilage atrophy
How much more load is there through the tibiofemoral joint of the knee compared to standing with:
Walking
Jumping
Running
Climbing stairs
Walking – 2-6 X body weight
Jumping – 7-9 X body weight
Running – 3-8 X body weight
Climbing stairs – 3-10 X body weight
Describe the pathogenesis of OA
Inflammation
Repair/remodelling of the cartilage
Pain
What occurs to the matrix components of cartilage in OA pathology
Proteoglycan-Fragmented by aggrecanases
Water-Increased by initial swelling, then lost
Collagen-Broken down by collagenases
Describe the pathology of EARLY OA
-Loss of proteoglycans
-Fibrillation of tissues
Features of established OA that early OA doesn’t have?
Established has:
-Fissuring
-Partial/full thickness cartilage loss
-Osteophytes, bone cysts, synovial inflammation
What are the risk factors for OA?
Age
Obesity
Mechanicals:Joint injury, joint misalignment
Genetics
Chondrodysplasias(e.g stickler syndrome)
Secondary joint damage due to inflammatory arthropathies e.g. rheumatoid arthritis
What percent of meniscal/ACL tear victims will develop OA in the next 5-10 years
~50%
Give some evidence for mechanical factors influencing the development of OA
Destabilising joint injuries increase risk of OA
Intra-articular fracture increases the risk of OA
Why does lack of aggrecanase stop the loss of cartilage after joint injury?
Cartilage is a biologically active process, dependent on aggrecanases
Outline the 2 pathways that lead to symptomatic OA
Abnormal joint + Normal load
Normal joint + Abnormal load
Leads to mechanical injury, leading to incorrect remodelling of cartilage
Then symptomatic OA
Do all OA cases progress?
No, some can remain at the same severity, or even remise
Demographically with age and sex where is OA more prevalent?
With greater age and more in women
Why are OA rates increasing?
Higher obesity levels, poorer diets that aren’t equipped to maintain cartilage health
How is OA diagnosed?
Clinically:
Stiffness
Pain on function
Crepitus, bony deformity
X-ray:
Osteophytes
Joint space narrowing
Bone cysts
Blood tests:
Normal CRP
Negative tests for RA
Other tests to exclude secondary causes
What are these?
Heberdens’ nodes, diagnostic of hand OA
Give 3 surgical options for OA treatment
Total joint replacement /‘arthroplasty’(hip or knee) is a highly effective treatment (best results when pain high, function poor, over 60, end stage radiographic disease)
Uni-compartmental replacement for the knee is possible
Trapeziectomy (removal of a thumb bone) is a good surgical treatment for base of thumb OA
Outline 2 new drugs targeted at treating OA and their effects
SyMOADs(Symptom modifying OA drug)-Treat pain+Improve function
DMOADs(Disease modifying OA drug)-Prevent/Slow early onset of OA
What are 3 requirements for clinical trials of new OA drugs
-Find drugs targeting the right sites
-Using the right population(Subgrouping+)
-Using the right outcome measurements(Imaging+patient reported outcomes)
