Equine Degenerative Joint Disease Flashcards
What are the two functions of joints?
- ) Provide pain free, almost frictionless motion
2. ) Transfer load of the forces
Osteoarthritis definition
- Progressive and permanent degeneration of articular cartilage accompanied by changes in the adjacent bone and soft tissues
Does acute loss of articular cartilage equal Degenerative joint disease?
- No
- It can lead to it, but does not equal it
What is the origin of DJD almost always?
- Traumatic in origin
Is DJD more often acute or a chronic injury?
- Chronic, repetitive injury
- Acute can happen too if they take a bad step; can result in a fracture too
6 parts of diarthrodial joints?
- Fibrous joint capsule
- Synovial membrane (villa)
- Intra-articular ligaments
- Articular cartilage
- Subchondral bone (shock absorption)
- Synovial fluid (Supplies nutrients to articular cartilage)
What is articular cartilage composed of primarily?
- 70% water
- Type II cartilage** (vs type I and type III being most common)
- Also: proteoglycan; glycoproteins; minerals, lipids, chondrocytes)
What determines the mechanical properties of cartilage?
- Composition of the extracellular matrix
- Avascular, aneurla, alymphatic
What regulates matrix maintenance and turnover in articular cartilage?
- Chondrocytes
Articular cartilage blood, nerve, and lymphatic supply?
- None - avascular, aneural, and alymphatic
Which is more dynamic: collagen turnover or proteoglycan turnover?
- Proteoglycan!
How do chondrocytes obtain their nutrients?
- Diffusion from the synovial fluid
- Also the medium through which metabolic waste products are removed
- Pumping action of weight bearing assists diffusion
- Glucose, oxygen, and amino acids must reach the cells by diffusion
Cartilage metabolism type
- Predominately anaerobic
What happens to articular cartilage in DJD?
- Disruption of normal balance between degradation and synthesis
- Degradation exceeds repair and DJD results
- Type II collagen turnover is slow
- Proteoglycans are rapidly exchanged
- Breakdown of collagen framework
- Reduction in proteoglycan content and alteration of proteoglycan structure
- Increase in water content (cell swelling)
- Increased degradative enzyme activity
What happens to the mechanical properties of articular cartilage in DJD?
- Softer in compression and weaker in tension
Healing
- Restoration of the structural integrity and function of the tissue after injury or disease (e.g. with bone)
Repair
- Replacement of damaged or lost cells and matrix with new cell and matrix (not necessarily restore the original structure of function of the tissue)
Capacity of cartilage to heal
- Very limited ability to heal
Intrinsic repair
- Relies on limited mitotic capability of chondrocytes and a somewhat ineffective increase in collagen and proteoglycan production
- Quite limited
Extrinsic repair***
- Comes from mesenchymal elements from subchondral bone participating in the formation of new connective tissue that may undergo some metaplastic change to form cartilage elements
What type of cartilage is laid down with extrinsic repair?
- Fibrocartilage
What influences extrinsic repair of articular cartilage?
- Depth of the lesion (full vs partial thickness)
- Size
- Location and relation to weight-bearing
- Age of the animal
Full vs partial thickness defect
- Repair takes longer for full thickness lesion
- Top of articular cartilage down to subchondral bone
- For partial thickness you may not need a full repair
- Partial thickness defects rarely completely heal, but may not compromise joint function
- Full thickness defects repair by ingrowth of subchondral fibrous tissue that may or may not undergo metaplasia to fibrocartilage
Location in relation to weight bearing
- DIRT lesions they cut down to healthy bone, but it’s not a big deal at the distal intermediate ridge of the tibia
- If they do the same thing with subchondral bone cysts or the lateral trochlear ridge, worse prognosis for developing arthritis
- Non weight bearing lesions heal faste rand may be less painful
Repair tissue that forms at 4 months of articular cartilage defects?
- Type I, then to type III
Tidemark and repair of articular cartilage defects
- Tidemark rarely reforms and the cartilage edges rarely re-attach
Fibrocartilage biomechanical properties
- Biomechanically unsuitable as a replacement bearing surface and has been shown to undergo mechanical failure with use
- CLINICALLY, may not result in compromise
- Greater chance of hitting itself with full thickness defect?
Osteoarthritis physical exam
- Heat
- Pain (lameness)
- Effusion
- Crepitus (bone crunch)
- Decreased range of motion
Distal intertarsal joint - why difficult to diagnose?
- ) not a high motion joint, so it’s challenging to notice decreased range of motion
- ) Joint doesn’t have a lot of synovial fluid, so not likely to be that effusive
Radiographic signs of osteoarthritis**
- ) Periarticular osteophyte formation
- ) Subchondral bone sclerosis
- ) Narrowing of the joint space
- ) Subchondral bone lysis
- ) Ankylosis
Diagnosing DJD
- Physical exam
- Analgesia exam (nerve blocks)
- Radiographic exam
What is he goal of rest, exercise, and physical therapy and medications?
- CANNOT REVERSE DAMAGE***
- Goal is to slow pathologic changes and prevent additional articular cartilage destruction
- Reduce lameness and restore joint function
Surgery for DJD - what are the goals?
- Prevention rather than treatment!!!
Aspects of surgery for DJD
- Fragment removal (if causing articular damage)
- Debride cartilage defect (if full thickness defect, it may be inflamed, degrading the synovial fluid, which will make it worse and worse)
- Internal fixation and joint reconstruction
- Lavage and decontamination of the joint (flush out inflammatory mediators)
- Debulk and debride soft tissues (if soft tissue inflammation)
- Arthrodesis (if too much soft tissue impeding the motion)
What is arthrodesis?
- Trying to facilitate ankylosis to the point where it fuses, as to remove the pain
- Often just involves going in and debriding cartilage
Intra-articular therapy ideal drug
- Promotes cartilage matrix
- Suppress catabolism
- Reduce synovial inflammation
- Normalize synovial fluid
- Relieve pain
- NOT ONE DRUG THAT DOES THIS
- Steroids can help reduce
- Be critical
What is adequan?
- Commercially available polysulfated glycosaminoglycan (PSGAG) for IA or IM use
Adequan role
- Considered chondroprotective
- MAY alter progression of DJD rather than simply provide a temporary palliation of clinical signs
When is adequan usually used?
- Traditionally in cases with extensive cartilage loss rather than synovitis
Adequan/PSGAG mechanism
- Unknown exactly
- Inhibits matrix metalloproteases (degradative enzyme), serine proteinases, lysosomal enzymes
- Decreases IL-1, prostaglandin (inflammation)
- Increases matrix synthesis
- Increases hyaluronan production
- Increases proteoglycan aggregation
- Decreases lameness
- Potentiate infection intra-articular, heparinoid
How do you give adequan?
- Intra-articular (may potentiate infection) or IM
Adverse effects of PSGAG
- ) heparinoid (may prolong bleeding times?)
- ) May potentiate infection whe administered intra-articular***
- Typically give wIM or IA with amikacin
What is cosequin?
- Oral PSGAG
- Nutraceuticals
- Combination of GAG and Chondroitin
Absorption of PSGAGs orally
- Little evidence to support oral absorption
Literature to support oral PSGAGs
- Little to no scientific data in horses, but good anecdotal reports
Hyaluronan
- Linear polysaccharide, a polyanionic nonsulfated glycosaminoglycan
(vs polysulfated)
Molecular mass of hyaluronan
- 1.5-6 million daltons
Functions of sodium hyaluronate?
- Increased proteoglycan aggregation
- Decreased IL-1 and TNF
- Decreased protein and cellular influx
- Decreased prostaglandins
- Scavenge free radicals
- No direct effect on arterial cart?
- Decrease lameness
- Prolong effects of corticosteroids
MOA of Hyaluronan
- Exact mechanism unknown
- Large #s of studies in humans and horses support efficacy
Half life of hyaluronan
- 96 hours for exogenous HA
- Less in diseased joints
- Anti-inflammatory effect
- May induce production of endogenous HA
Corticosteroids for DJD***
- Used to treat various arthropathies for the last 50 years
- At high doses may induce cartilage damage by altering cartilage matrix metabolism
- Most steroids are rapidly cleared ,but may exhibit longer effects
Corticosteroids and racehorses
- MUST BE AWARE OF withdrawal times
How are corticosteroid effects exerted?
- Interaction with steroid specific receptors in the cytoplasm
How long to see effects from corticosteroids?
- Onset of action is immediate
- Completion of all steps necessary to realize a physiologic effects may take several hours to several days
How do corticosteroids work?
- Inhibit movement of inflammatory cells into a site of inflammation
- Alter neutrophil function
- Inhibit prostaglandin formation and inhibit phospholipase A2
Intra-articular corticosteroids action
- Anti-inflammatory
- Inhibit chondrocytes, osteoblasts, fibroblasts (negative impact)
- Lysosomal membranes
- Decrease neutrophil margination and diapedesis
- Inhibit Cyclooxygenase and lipoxygenase
- Decrease prostaglandins, matrix metalloproteases, and cytokines
Detection time for intra-articular corticosteroids
- Relatively short
Half life of methylprednisolone acetate (Depo medrol) (IA steroid)
- 36-72 hr half life
Negative side effects of methylprednisolone acetate (IA steroid)
- Chondrocyte necrosis, decreased proteoglycan and collagen synthesis, thinning, and fibrillation
- Dose dependent
Other effects of methylprednisolone acetate (IA steroid)
- Increased synovial fluid hyaluronic and prostaglandin (degradation)
- Increased cartilage trauma
- remote joint effects
- Decreased PGE2
- No effect on lameness score
Triamcinolone acetonide duration
- Intermediate (12-36 hours)
Triamcinolone acetonide intra-articular steroid
- Decreased lameness
- Decrease synovial fluid protein
- Increased hyaluronate and PG
- Increased synovial fluid quality
- Decreased inflammatory cells
- Impaired cartilage morphology
- MIGHT BE LAMINITIS?
Betamethasone sodium phosphate and acetate
- Long acting (36-72 hr half life) but short acting component
Betamethasone sodium phoshphate and acetate effects
- No significant decrease in cartilage proteoglycan
- No significant difference in lameness
Adverse effects of IA steroids
- Steroid arthropathy
- Post injection flare
- Potentiation of infection
- Delayed appearance of clinical signs
Autologous conditioned serum (ACS) (Mostly FYI)
- Interleukin-1 receptor antagonist protein
- Shown to increase anti-inflammatory cytokines and growth factors
- Decrease inflammation in joint
- No adverse side effects reported
- Venous blood incubated with glass beads for 24 hours
- Serum centrifuged and filtered then injected into specific joint
Mesenchymal stem cells as tx for DJD
- Differentiate into multiple different cell types and tissues
- may be helpful in cases with joint instability or meniscal damage
- Some evidence of beneficial effects in cases of osteoarthritis
