OA Flashcards
Describe the 3 layers/zones of cartilage above the tidemark.
- tangential layer/superficial zone: reserve chondrocytes are here, they are smaller and flattened
- transitional layer/middle zone: where chondrocytes start to proliferate, they are bigger and rounder
- radial layer/deep zone: chondrocytes hypertrophy and become more rounded, they form into columns and stacks
What is found below the tidemark in cartilage?
- calcified zone
- subchondral zone
- cancellous bone
What types of collagen are found in the ECM of cartilage? Which is the main type?
Type II collagen is the main type - it is found in all layers, but most is in the superficial layer
Type X is found in the calcified deep layers
There is also collagen type I among others
Describe the structure of proteoglycans and state their role.
proteoglycans have a core protein (hyaluronan) and glycosaminoglycan side chains (keratin sulphate and chondroitin sulphate)
role: regulate compressibility and absorb shock
Why is pain not felt when cartilage alone is damaged?
There is no nerve supply
- only feel pain once synovial and bone are affected
What is the orientation of the collagen fibres in the different layers of cartilage?
Superficially: parallel with surface, highest tensile properties allows gliding
Intermediate: criss-crossed which allows for compression
Deep: perpendicular to follow the stacks of chondrocytes
What joints are mainly affected in OA?
Larger, weight-bearing joints
Knees, hips, but also small hand joints
Does OA usually present unilaterally or bilaterally?
Unilaterally
What are the symptoms of OA?
Joint pain (with use) morning stiffness <30 minutes joint instability or buckling loss of function crepitus on motion
What are the signs of OA?
bony enlargement at affected joints limited range of motion muscle atrophy/weakness malalignment and/or joint deformity crepitus on motion
What are the main radiological and biochemical features of OA?
Radiological:
- narrowing of joint space
- osteophytes
- subchondral sclerosis
- subchondral cysts
- vascular engorgement
- trabecular fracture
Biochemical:
- synovitis
- hyaluronic acid depolymerised
What are the systemic risk factors for OA?
- genetics
- increasing age
- female gender
- diet
- BMD
- post-menopausal HRT
What are the intrinsic risk factors for OA?
- past joint surgery
- infection
- congenital abnormalities, e.g. -joint Mal-alignment
What are the extrinsic risk factors for OA?
- past joint surgery
- occupational exposures
- physical activity levels
- BMI
In the development of OA, what is increasingly broken down/produced less?
Aggrecan and collagen type II
What substances are increased in the ECM in the development of OA?
Matrix Metalloproteinases (MMPs) A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)
What does the break down of collagen result in the release of?
Pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha
What is the response to the necrosis of chondrocytes, breakdown of collagen and release of pro-inflammatory cytokines in the synovial space? What is the effect of this response?
influx of synovial macrophages and immune cells (such as TH cells)
- these contribute towards inflammation = synovitis
What is the reason for the pain felt in OA?
Pain results from inflammation of the synovium and damage to bone as these structures are innervated
**not due to erosion of cartilage directly
Why does bone thicken (subchondral sclerosis) in OA?
When bone is exposed it suffers from microfractures
Hyaluronic acid from synovial fluid can also leak in causing the cracks to widen
This leads to an increase in osteoblastic activity and new bone formation
(I think this is right, not 100% sure lol)
What are the 3 phases of degeneration that bones in OA undergo macroscopically?
- Fibrillation
- Erosion and cracking
- Eburnation
- complete loss of cartilage
- completely exposed bone becomes polished
What microscopic changes occur in the cartilage in OA?
- chondrocyte necrosis - more marked in superficial layers
- focal clumps/clones of chondrocytes - increased local proliferation results in large isogenic clusters
- change from hyaline cartilage (type II) to fibrocartilage (type I) - this reduces the thickness of the cartilage so there is TIDEMARK DUPLICATION + thickening of calcified cartilage
What biochemical changes are seen in the cartilage in OA?
- Early stages: cartilage thickens and swells as cartilage is more porous therefore water can leak in and out despite less hyaluronan to hold onto the water
- loss of proteoglycans therefore cartilage is less compressible
- collagen network breaks down as enzymes are released from stressed chondrocytes and synovial membrane cells (MMPs, collagenases, ADAMTS)
- cartilage softens (chondromalacia) and progresses to fibrillation
What is HMGB2 and how is it associated with OA?
- HMGB2 = high mobility group protein 2 (chromatin protein)
- It is expressed in the superficial zone of cartialge
- It supports chondrocyte survival and regulates specific differentiation status of the superficial zone cells
- loss of HMGB2 = superficial zone cell death, loss of progenitor cells and reduced synthesis of ECM components
What are the pharmacological options for treating OA?
- Topical analgesics:
- topical capsaicin, topical NSAIDs and methylsalicylate cream - Oral analgesic:
- Paracetamol usually 1st choice
- Then move onto a NSAID or COX-2 inhibitor –> should be prescribed at the lowest effective dose and with a PPI - intra-articular injections:
- anti-inflammatory properties of corticosteroid reduced synovitis and relieves pain
What are some alternative/adjunct treatment for OA?
- Exercise
- local muscle strengthening
- general aerobic fitness - Diet and weight loss
- less loading of the joints
- adipocytes/kines are thought to be pro-inflammatory - Suitable footwear, aids, walking devices
- Transcutaneous nerve stimulation
- Thermotherapy
- Nutraceuticals
- increase intake of omega-3 rich foods (anti-inflammatory)
When would an OA patient be referred to an orthopaedic specialist?
If the condition is impacting QOL –> waking at night due to pain
Describe the procedure of arthroscopic washout and debridement plus micro fracture. What kind of patients does this work best for?
- drilling into subchondral/ exposed bone and bone marrow pluripotent stem cells
- this stimulates repair of the articular cartilage
- cartilage should recover in 4-6 months
- makes fibrocartilage rather than hyaline (still better than no repair)
- people <40 with recent cartilage injury will have the best results
- people who are not overweight will have better results
What is Viscosupplementation?
- replaces synovial fluid with a substitute
- MOA: returns higher molecular weight hyaluronans and increases viscosity (protective for cartilage)
- provides direct analgesic effect
What are the advantages of Viscosupplementation?
- works well at all stages of OA
- improves patient assessed pain
- well-tolerated
- long-term effectiveness
What are the disadvantages of Viscosupplementation?
- severe OA may not respond as well
- some local adverse effects at injection site
Where are sources of chondrocytes for grafting?
- rib costochondral process
- non-damaged part of joint
- cartilage implants from young individuals
What is mosiacplasty?
Osteochondral grafting
- take undamaged cartilage from less weight-bearing regions plus the underlying bone and move to OA region
- at 1 year up to 88% of pts have good to excellent outcomes
What are the two different kinds of osteotomy?
Opening wedge = adding material
Closing wedge = removing a wedge of bone
Where is the osteotomy performed for:
- genus valgum
- genus varus
- genus valgum = knock knees - perform on the femur
2. genus varus = bow-legged - perform on tibia
What are the main complications associated with joint replacement?
- aseptic loosening
- instability
- infection
- pain
- peri-prosthetic fracture
- component failure
