Lecture 2: Joint therapies

Describe the inflammatory cascade that results in osteoarthritis.

Osteoarthritis can result from abnormal stresses on normal cartilage (e.g., due to joint instability or injury like an OC fragment) or normal stresses on abnormal cartilage (e.g., due to OCD lesions or subchondral bone disease). Both scenarios lead to the breakdown of articular cartilage.

The body responds to trauma or wear and tear by activating pathways involving IL-1 and TNF-alpha. These cytokines then stimulate proteolytic enzymes such as aggrecanases and metalloproteinases, as well as prostaglandins. These enzymes work to deplete the cartilage matrix and subchondral bone, setting up the cycle of osteoarthritis

Describe symptom vs disease modifying effects of joint therapies.

Symptom-Modifying Effect: These therapies change how the horse looks and feels by alleviating clinical signs such as lameness, pain (improving flexion test), and joint effusion. They aim to make the horse feel better without necessarily altering the underlying disease process. Examples include NSAIDs like Bute and Flunixin and corticosteroids.

Disease-Modifying Effect: These therapies aim to stop or slow down the processes that degrade cartilage and potentially enhance repair processes. They target the cartilage, synovial membrane, or subchondral bone. Examples include Hyaluronic Acid (HA), Polysulfated Glycosaminoglycan (PSGAG), Pentosan, potentially Triamcinolone (a corticosteroid), Polyacrylamide Hydrogels, and Orthobiologics (PRP, IRAP, Pro-Stride, stem cells). Some therapies, like Firocoxib (a COX-2 selective NSAID), and possibly HA, PSGAG, and Pentosan, may have both symptom and disease-modifying effects.

Describe the mechanism of action of Steroids.

Corticosteroids exert their anti-inflammatory effects by acting high up in the inflammatory cascade, inhibiting the production of arachidonic acid from phospholipids in cell membranes. This is upstream of the cyclooxygenase (COX) enzymes. By reducing arachidonic acid availability, steroids reduce the production of prostaglandins, prostacyclins, and thromboxanes, which are key mediators of inflammation.

Intra-articularly administered corticosteroids like Triamcinolone (shorter-acting, often used in high-motion joints) and Methylprednisolone Acetate (MPA or Depo-Medrol) (longer-acting, often used in low-motion joints) aim to reduce inflammation within the joint. While effective at reducing inflammation and improving synovial membrane health, some corticosteroids, particularly MPA, may not be cartilage-friendly and could potentially halt repair processes. Triamcinolone is considered more joint-friendly in some studies.

Describe the mechanism of action of HA (Hyaluronic Acid).

Hyaluronic acid (HA) is a major component of the cartilage matrix and synovial fluid. Its mechanisms of action include:

Viscosupplementation: Intra-articular HA aims to enhance the quality (viscosity) of the joint fluid and potentially the joint membrane.

Providing Building Blocks: Systemic (IV) administration aims to supply building blocks for the cartilage matrix.

Anti-inflammatory Properties: HA appears to have anti-inflammatory effects, potentially by counteracting the effects of inflammatory cytokines like IL-1. Studies suggest that HA can improve lameness scores and may work better than placebo. Combining HA with corticosteroids like Triamcinolone may have a beneficial effect on cartilage by increasing glucosamine and glycogen and stopping catabolic effects. Although HA is cleared from the joint relatively quickly (within 48 hours), it seems to provide clinical benefits.

Describe the mechanism of action of Polyacrylamide Hydrogels.

Polyacrylamide hydrogels are synthetic polymers forming a 3D network that traps water, thereby increasing the viscosity of the joint fluid and supporting the joint membrane. These hydrogels, such as Arthramid Vet and Naltrex, are designed to be biocompatible and do not degrade back into acrylamide.

Specific mechanisms include:

Increased Joint Capsule Elasticity: Arthramid Vet has been found to increase the elasticity of the joint capsule. This is particularly beneficial for conditions like synovitis or capsulitis in young horses.

Increased Synovial Fluid Viscosity: Other polyacrylamide hydrogels primarily work by increasing the thickness of the synovial fluid, providing cushioning and lubrication.

Clinical studies suggest that polyacrylamide hydrogels can lead to a significant improvement in lameness and have long-lasting symptom-modifying effects, potentially lasting up to 24 months. Safety studies indicate a low incidence of adverse events, primarily transient joint flares

Describe the mechanism of action of Orthobiologics.

Orthobiologics, also known as regenerative or biological therapies, aim to harness the horse's own regenerative potential to treat joint disease. These therapies are derived from the horse's body, primarily blood products (PRP, IRAP/ACS, APS/Pro-Stride) or bone marrow/fat (stem cells).

Their proposed mechanisms of action include:

Platelet-Rich Plasma (PRP): Concentrated platelets release growth factors that can modulate inflammation and promote healing. Studies in humans suggest a prolonged response compared to corticosteroids.

Autologous Conditioned Serum (ACS/IRAP) and Autologous Protein Solution (APS/Pro-Stride): These blood-derived products contain anti-inflammatory cytokines (like interleukin-1 receptor antagonist) that can counteract the damaging effects of inflammatory mediators in the joint. Studies have shown improvement in lameness and reduced signs of inflammation and cartilage damage.

Stem Cells (from bone marrow or fat): These progenitor cells are thought to orchestrate or dampen the inflammatory process and potentially contribute to tissue repair. While showing promise, the science behind stem cell therapies in horses is still evolving, and more research is needed.

Many practitioners believe orthobiologics provide a more durable response and are a safe treatment option due to their autologous nature. They are generally considered symptom-modifying, and some evidence suggests they may also have disease-modifying effect

NSAIDs: How do they work?

Inhibit COX enzymes, reducing prostaglandins and inflammation.

Bute & Flunixin: Symptom or disease modifying?

Primarily symptom modifying.

Firocoxib: What's special about it?

COX-2 selective, potentially safer.

Corticosteroids (IA): Main action?

Reduce inflammation in the joint.

Triamcinolone: Best for what joints?

High-motion joints. May be more joint-friendly.

MPA (Depo-Medrol): Best for what joints?

Low-motion joints (e.g., hocks).

IA Corticosteroids: Risk to cartilage?

May halt repair, especially MPA.

IA Corticosteroids: Injection frequency?

Around every six months.

IA Corticosteroids: Laminitis risk?

Low risk in healthy horses; caution in at-risk horses.

IA Corticosteroids: Infection risk?

Minimized by sterile technique. Avoid Amikacin.

Hyaluronic Acid (HA): How does it help?

Viscosupplementation, may reduce inflammation.

HA (IV): Purpose?

Supply building blocks for cartilage.

PSGAG (Adequan) & Pentosan: Administration?

Systemic (IM/IV) or intra-articular.

PSGAG & Pentosan: Effect on disease?

May be disease and symptom modifying.

Polyacrylamide Hydrogels: Main function?

Increase synovial fluid viscosity.

Arthramid Vet: Special action?

Increases joint capsule elasticity.

Polyacrylamide Hydrogels: How long do effects last?

Potentially up to 24 months.

Orthobiologics (PRP, IRAP, Pro-Stride): What are they?

Blood-derived therapies using horse's own cells.

Orthobiologics: Main goal?

Harness regenerative potential.

Stem Cells: Source?

Bone marrow or fat.

Stem Cells: Autologous vs. Allogenic?

Autologous: From the same horse. Allogenic: From a different horse.

What is the primary goal of joint therapies in horses with osteoarthritis? a) To cure osteoarthritis completely. b) To solely focus on pain relief. c) To modify the ongoing process of arthritis and/or alleviate symptoms. d) To prevent horses from ever developing osteoarthritis.

c) To modify the ongoing process of arthritis and/or alleviate symptoms.

Which of the following is considered to have a symptom-modifying effect on equine joints? a) Polysulfated glycosaminoglycan. b) Platelet-rich plasma (PRP). c) Phenylbutazone (Bute). d) Stem cell therapy.

c) Phenylbutazone (Bute)

According to the professor, what might be a reason for osteoarthritis to develop in a horse? a) Consuming too much protein in their diet. b) Regular exercise on soft surfaces. c) Abnormal stresses on normal cartilage due to a joint instability. d) A lack of exposure to sunlight.

c) Abnormal stresses on normal cartilage due to a joint instability.

Which of the following enzymes is involved in the breakdown of cartilage in osteoarthritis? a) Lipoxygenase. b) Metalloproteinases. c) Creatine kinase. d) Amylase.

b) Metalloproteinases.

Corticosteroids primarily work by acting at what level of the inflammatory pathway? a) By inhibiting cyclooxygenase enzymes. b) By directly repairing damaged cartilage. c) At a high level, influencing the production of arachidonic acid from phospholipids. d) By increasing the viscosity of synovial fluid.

c) At a high level, influencing the production of arachidonic acid from phospholipids.

Which intra-articular corticosteroid is generally preferred for high-motion joints? a) Methylprednisolone Acetate (MPA). b) Triamcinolone. c) Betamethasone. d) Dexamethasone.

b) Triamcinolone.

Which intra-articular corticosteroid is often used in low-motion joints like the lower hock? a) Triamcinolone. b) Betamethasone. c) Methylprednisolone Acetate (MPA). d) Isoflupredone Acetate.

c) Methylprednisolone Acetate (MPA).

According to the sources, what is a potential negative effect of Methylprednisolone Acetate (MPA) on joints? a) It has a very short duration of action. b) It is highly effective in repairing cartilage. c) It is possibly harmful to the joint. d) It has no effect on the synovial membrane.

c) It is possibly harmful to the joint.

What is the primary proposed mechanism of action for intra-articular hyaluronic acid (HA)? a) To directly stimulate cartilage repair. b) To suppress the immune system in the joint. c) Viscosupplementation, enhancing the quality of joint fluid. d) To cause an inflammatory response that triggers healing.

c) Viscosupplementation, enhancing the quality of joint fluid

Polysulfated glycosaminoglycan (PSGAG) like Adequan is typically administered via which route for joint therapy in horses? a) Intra-articularly only. b) Intravenously only. c) Intramuscularly (IM). d) Orally.

c) Intramuscularly (IM).

Polyacrylamide hydrogels like Arthramid Vet primarily function by: a) Directly stimulating chondrocyte proliferation. b) Inhibiting all inflammatory cytokines in the joint. c) Trapping water and increasing the viscosity of joint fluid. d) Degrading into healing components within the joint.

c) Trapping water and increasing the viscosity of joint fluid.

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Which of the following is a blood-derived orthobiologic therapy used in equine joint treatment? a) Hyaluronic acid. b) Polysulfated glycosaminoglycan. c) Platelet-Rich Plasma (PRP). d) Polyacrylamide hydrogel.

c) Platelet-Rich Plasma (PRP).

Autologous Conditioned Serum (ACS) / IRAP works by: a) Directly repairing damaged cartilage matrix. b) Increasing the number of platelets in the joint. c) Providing antagonists to inflammatory cytokines like interleukin-1. d) Stimulating stem cell migration to the joint.

c) Providing antagonists to inflammatory cytokines like interleukin-1.

What is a potential concern associated with injecting corticosteroids into a horse's joint? a) Excessive cartilage growth. b) Increased production of hyaluronic acid. c) Suppression of the local immune system. d) Immediate and permanent pain relief.

c) Suppression of the local immune system.

According to the professor, what is the current recommendation regarding the use of Amikacin in combination with intra-articular therapies? a) It is highly recommended to prevent joint infections. b) It should always be used with corticosteroids for optimal effect. c) It should likely be avoided due to potential harm to chondrocytes and the synovial lining. d) There is no scientific consensus on its use.

c) It should likely be avoided due to potential harm to chondrocytes and the synovial lining.

Following an intra-articular injection, what is a common recommendation regarding the horse's activity level? a) Immediate return to full work. b) Increased exercise to promote circulation. c) A period of rest in a stall or small paddock. d) Continuous hand-walking for several days

c) A period of rest in a stall or small paddock.

What is a potential risk factor that may increase a horse's susceptibility to laminitis following intra-articular corticosteroid injection? a) Young age. b) Regular farrier care. c) Underlying metabolic syndrome or insulin dysregulation. d) A diet high in forage.

c) Underlying metabolic syndrome or insulin dysregulation.

Stem cells used for joint therapy can be sourced from: a) Synovial fluid only. b) Cartilage tissue only. c) Bone marrow or fat. d) Hoof tissue.

c) Bone marrow or fat.

According to the conclusions in the "Joint Therapies.pdf" source, which type of intra-articular therapy seems to have potent and long-lasting symptom-modifying effects? a) Corticosteroids. b) Hyaluronic acid. c) Orthobiologics. d) Polyacrylamide hydrogels (PAAG).

d) Polyacrylamide hydrogels (PAAG).