Degenerative joint disease (DJD) Flashcards
(41 cards)
1
Q
What is DJD?
A
- the end stage of joint disease
- one of the most common orthopaedic conditions vets deal with in practice
- incurable, but ideally temporarily manageable
- degeneration of articular cartilage
- bone changes (OA) -new bone formation and bone lysis
2
Q
Contents - cartilage
A
- 75% water
- 15% type 2 collagen
- 8% PGs
3
Q
What conditions lead to DJD? 5
A
- TRAUMA (acute, repetitive)
- INFECTIOUS INFLAMMATION (septic arthritis)
- NON-INFECTIOUS INFLAMMATION
- DEVELOPMENTAL DISEASE (dysplasia, angular limb deformity, flexural limb deformity, osteochondrosis)
- OTHER
4
Q
Outline pathophysiology of DJD
A
- AC: failure of homeostasis (cartilage breakdown products, MMPs, and catabolic cytokines (IL-1, IL-6, TNF)
- SYNOVIAL MEMBRANE: Pgs, leukotrienes, neuropeptides, cytokines
- SUBCHONDRAL BONE: (chronic remodelling) altered load absorption - cartilage damage, inflammatory mediators (IL-1, TNF)
5
Q
What causes pain in arthritis?
A
- no pain Rs in cartilage
- pain Rs in joint capsule (synovitis, joint distension)
- exposure of sunchondral bone
6
Q
What is the role of soft tissues in cartilage degradation?
A
- synoviocytes release mediators and enzymes (PGs, cytokines, MMPs)
- increased levels of inflammatory mediators measured in joint fluid
7
Q
How well do radiographic signs of OA correlate with CS?
A
poorly
8
Q
What to look for on clinical exam
A
- weight and BCS
- LAMENESS EXAM:
- ID
- scoring
- localise
- palpation/manipulation of joint
- pain/heat/ swelling/crepitus
- joint thickening/ effusion
- reduced ROM
- mm atrophy
- local analgesia
- synovial fluid analysis (LA often unspecific)
- diagnostic imaging: radiograph (plain/contrast), ultrasound, MRI/CT
- arthroscopy: synovial biopsy sometimes
9
Q
What is more specific than peripheral nn blocks in large animals?
A
intraarticular analgesia
10
Q
What should you do if you have a positive digital nerve block?
A
return on 2 separate occasions to block DIPJ and the navicular bursa
11
Q
List radiographic features to look for when suspecting OA - 3
A
- osteophytes
- soft tissues (soft tissue, effusion)
- subchondral bone sclerosis
12
Q
Goals - arthritis tx
A
- pain reduction
- stop inflammation (decrease mediator secretion)
- chondroprotection (disease modification = to arrest/slow down cartilage degeneration, but EBVM lacking)
- established OA cannot be fully cured
13
Q
Tx strategies - arthritis
A
- weight control
- exercise modification/ physio
- strategic analgesia (achieve acceptable level of exercise)
- joint supplements (nutraceuticals, disease modification)
- novel tx concepts
- salvage procedures (if all else fails)
14
Q
Tx - arthritis flare-ups - 3
A
- initial analgesia (5-10d)
- gradually resume controlled exercise
- swimming/hydrotherapy
15
Q
Medical arthritis tx - large animals
A
- NSAIDs
- I/A corticosteroids
- GAGs
- sodium hyaluronate
- supplements (chondroitin sulphate, glucosamine)
- IL-1 antagonist protein
- Tiludronate (Tildren): selected conditions
16
Q
What do corticosteroids block?
A
- PLPA2 (i.e. pain, swelling, cartilage degradation, heat)
- COX
- cartilage-degrading enzymes (MMP-13,3,1 and aggrecanase 1)
17
Q
What do NSAIDs block?
A
COX
18
Q
What is commonest medication for orthopaedic problems?
A
NSAIDs (cheap adn efficient)
19
Q
Side effects - NSAIDs
A
- GI ulcer
- nephritis (with sensitive animals)
- PLE (with chronic ulcers)
- negative influence on cartilage and bone metabolism
20
Q
Why is ketoprofen popular in horses?
A
because more COX1 selective in horses. used often in foals, v expensive in adults because of dose required
21
Q
Outline corticosteroids in tx of arthritis
A
- often in horses
- most potent anti-inflammatory drugs (inflammatory cells and humoral mediators)
22
Q
Side effects- IA corticosteroids
A
- negative effects on cartilage metabolism and healing
- data controversial
- decreased PG synthesis and organisation
- increased risk of iatrogenic joint infections (temporary shut down of inflammatory defence mechanisms)
- laminitis?
23
Q
What dictates drug choice and dose? 4
A
- joint volume
- severity of inflammation
- # joints to tx
- personal preference
24
Q
List options for IA corticosteroids
A
- bethamethasone
- triamcinolone acetonide
- flumethasone
- isoflupedone acetate
- methylprednisolone acetate
25
Describe mechanism of polysulphated GAGs in horses - 3
- MMP inhibition
- stimulates HA production
- stimulates matrix synthesis
26
Use of GAGs
- higher concentration
- increased risk of sepsis
- non-septic inflammation (flare)
- licensing
- only licensed for IM injection (use higher dose if going IA)
27
Name 2 types of GAG used in horses for arthritis
- polysulphated GAGs (Adequan) = from bovine lung and trachea
- pentosan polysulphate (Catrophen) = from beechwood hemicellulose
28
Mechanism -pentosan polysulphate
- stimulates cartilage matrix synthesis
- stimulates HA syntehsis
- MMP inhibition
- inhibits inflammatory mediators
- mobilise thrombi and fibrin in synovium
- mobilise lipids and cholesterol in BVs
- inhibits platelet aggregation and clotting
- increase plasma lipase levels
29
Why is sodium hyaluronate good to give to horses?
Major structural component:
- Articular cartilage matrix (from chondrocytes)
- Synovium (by type B synoviocytes)
Anti-inflammatory function (either by steric hindrance or chemotactic response)
30
Mechanism - exogenous sodium hyaluronate in horses
- speculative
- lubrication
- anti-inflammatory activity
- activation of cell receptors
- supplementation of depleted endogenous HA
- stimulation of endogenous HA synthesis
* important that molecular weight is > 5* 10^2kDa
31
Administration - sodium hyaluronate
- IA
- IV
- Per os (unknown bioavailability)
32
Mechanism - neutraceutical supplements
- stimulate cartilage matrix synthesis
- MMP inhibition
- reduce inflammatory mediators
33
Name 3 matrix GAG supplements
- gluosamine (3 forms; HCl, So4, N-acetyl-D-glucosamine)
- chondroitin sulphate (small molecules important for degradation in GIT mucosa)
- glucosamine/ chondroitin sulphate combination (effect may be better than individual effect)
34
What is green-lipped mussel extract?
- from edible shellfish (NZ)
- neutraceutical supplement
- anti-inflammatory
- chondroitin sulphate source
- unique combination of fatty aas
- minerals
- vitamins
35
What is methylsulphonylmethan (MSM)?
- sulphur source (usually enough in diet) for collagen and matrix metabolsim
- derivate from DMSO
- mechanism: unknown, no effect on inflammation, may be analgesic in people
36
What is devil's claw?
= iridoid glycosides
MECHANISM: decrease inflammatory mediators in people, no EBVM. Used in traditional african medicine (arthritis, fever, skin conditions, GI disease)
37
What is IRAP?
= IL-1 Receptor Antagonist Protein
- for equine OA
- directly blocks effects of IL-1
- decreased inflammation in experimental synovitis
- no controlled large scale clinical studies (horse)
- therapeutic success in many cases refractory to steroids
38
What does IL-1 do?
- key inflammatory mediator in OA
| - stimulates cartilage-degrading enzymes (MMPs, aggrecanase)
39
What is ACS?
= Autologous Conditioned Serum
- for equine OA
- culture patient blood in special syringe (chromium-sulphate soaked glass beeds)
- up-regulation of IRAP and other anti-inflammatory mediators
- IA administration
- serum can be stored frozen (for serial IA injections)
40
What is Tiludronate (Tildren)?
- non-nitrogenous biphosphonate: inhibition of bone resorption (osteoclast apoptosis), anti-inflammatory properties
- Europe - licensed for horses, distal tarsal OA, navicular disease, side effect may be colic so give as CRI over 30 mintues
41
Name surgical tx for OA
- excision arthroplasty (SA + small ponies)
- arthrodesis (horse pastern, distal tarsus, fetlock, carpus; often salvage procedure)
- total joint replacement (SA)
