Pathophysiology of OA (not done)

What is the pathogenesis of OA?

Catabolic processes overwhelm anabolic causing whole joint diseases like synovitis, subchondral bone sclerosis, articular cartilage degradation

What leads a major role in the pathogenesis of OA?

Synovitis b/c it leads to cartilage fibrillation, chondrocyte necrosis, loss of GAGs, formation of osteophytes and exostoses

Also increases inflammatory mediators

What is articular cartilage?

Cover subchondral bone to create a frictionless surface

It is poorly cellular with the main cell type being chondrocytes

What is the ECM made of?

Water

Cartilage

Proteglycans

What does collage do in the ECM?

Tensile strength

What does proteoglycans do in the ECM?

Stiffness and resilience

What are the zones of articular cartilage?

Superficial

Intermediate

Deep

Calcified cartilage

What are proteoglycans in the ECM?

35% dry weight of articular cartilage there are large aggregating and small proteoglycans

What is aggrecan?

Proteoglycan that is the core protein backbone with GAGs attached radially

Negatively charged so they repel each other providing compressive stiffness

How do you proteoglycans resist compressive force?

By attracting water

What happens to articular cartilage in an OA joint?

Gross fibrillation and softening

Chondrocytes cannot repair enough so catabolic changes occur

Fragmentation or flapping

Calcification and osteophyte formation

What is the only way to repair tissue during OA when anabolism is overwhelemed?

Fibrocartilage

Describe subchondral bone in a healthy joint

Has compact and trabecular bone

Rich in vessels and nerves

Very metabolically active and constantly undergoes remodeling in response to loading

What happens to subchondral bone in an OA joint during early phases of remodeling?

Thinning and increased porosity

What happens to subchondral bone in an OA joint during late phases of remodeling?

Thickening and stiff

What is the joint capsule in a healthy joint?

Has fibrous outer capsule and inner synovium

What does the fibrous outer capsule do in the joint?

Provides stability and aids in proprioception

Describe a healthy synovium

Highly innervated and vascular in the subintimal

In the intimal there are few cells to allow ultrafiltration of plasma to maintain synovial fluid

Has 3 types of synoviocytes

What is a type A synoviocyte?

Phagocytic function

What is a type B synoviocyte?

Produce and excrete proteins and nonsulfated GAGS

What is a type C synoviocyte?

Intermediate cell type

What is synovial fluid in a healthy joint?

Ultrafiltrate of plasma

Provides lubrication and nutrients of articular cartilage

Low cellular component with mostly lymphocytes and mononuclear cells

Describe synovial fluid in an OA joint

Decreased hyaluronan decreasing viscosity

Increased pro-inflammatory mediators

TNCC can or can not increase

Increase in biomarkers like CS846, CPII, and Col but not measured clinically

What is IL-1Beta?

Major proinflammatory cytokine in OA

Expressed in cartilage and responsible for cartilage damage

Stimulates inducible NO synthase and COX-2

What is PGE2?

Product of arachidonic acid pathway and proinflammatory

Causes degradation of proteoglycans, inhibit proteoglycan synthesis, bone demineralization, vasodilation, and enhanced pain perception

What does iNOS do?

Stimulates release of NO from chondrocytes inducing matrix degradation and chondrocyte apoptosis

Proinflammatory

What are Aggrecanases?

Proinflammatory proteolytic enzyme that belongs to the ADAMTS family

Causes aggrecan degradation in cartilage

What are the C/S of OA?

Lameness/pain

Decreased ROM

Effusion

How do you diagnose OA?

PE/lameness exam

Blocking to localize

Imaging like rads, US, CT, MRI, arthroscopy

What are the goals of OA treatment?

Reducing pain (lameness)

Minimizing progression of joint deterioration

Reduce inflammation

How do you manage OA?

Exercise modification to encourage a lot of lighter work and rarely complete stall rest

Therapeutic farriery

What medical therapies are used for OA?

NSAIDs, steroids, polysulfated glycosaminolycan, sodium hyaluronate, biologics, platelet-rich plasma, bisphonphonates, lubricants, oral GAGs

What is the MOA of NSAIDs?

Inhibit production of prostaglandins and thromboxans by blocking COX

What is COX-1?

Endogenous good and will be impacted by nonspecific COX inhibitors

What is COX-2?

BAD Impacted by nonspecific and COX-2 inhibitors

How can you give NSAIDs?

IV, PO, topical (diclofenac)

What are side effects of NSAIDs?

GI ulcer

Renal papillary necrosis

Alters GI microbiome

What are the bisphosphonates?

Tildren and Osphos

What are bisphosphonates used for?

Off-label to manage pain by preventing bone resorption and inhibit osteoclasts

What are side effects of bisphosphonates?

Colic, renal injury, only use if horse >4years old

Cannot combine with NSAIDs

What supplements and adjunctive therapies are used?

Oral supplements like CS, GU, HA

Adjunctive therapies like ESWT, bodywork, or acupuncture