Osteoarthritis and Osteochondrosis Lecture Quiz

Learning Outcomes for Osteoarthritis and Osteochondrosis Lecture

• Students should be able to describe the pathological processes leading to osteochondrosis.
• Students should be able to provide examples of arthritic diseases, their symptoms, clinical consequences, and risk factors.
• Students should be able to describe the pathophysiological mechanisms underlying osteoarthritis.
• Students should be able to identify scoring methods for categorizing cartilage damage and lameness/pain behavior in animals.

Osteochondrosis

• A skeletal disease affecting bone growth in growing animals (developmental).
• Results from a non-infectious disturbance in endochondral ossification.
• Common in pigs, horses, dogs, cattle, sheep, poultry, and humans.

Bone Growth (Ossification Recap)

• Chondrocytes (cartilage cells) proliferate in the outer edge of epiphyseal plates next to the epiphysis.
• As new chondrocytes are added, old chondrocytes on the diaphyseal border enlarge.
• This leads to temporary widening of the epiphyseal plate.
• Matrix around old chondrocytes calcifies and die due to lack of oxygen and nutrients.
• Osteoclasts remove dead chondrocytes/calcified matrix.
• Osteoblasts from the diaphysis invade the space and produce new bone and blood supply to the epiphyseal plate.
• The epiphyseal plate returns to its original thickness with new chondrocytes.

Cartilage Canals

• Picture/diagram showing cartilage canals.
• Cartilage canals in articular cartilage.

Osteochondrosis - Stages

• Stage A: Healthy cartilage in young animals, highly vascularized via cartilage canals.
• Stages B and C: Blood supply disruption causes ischemic necrosis of surrounding cartilage (osteochondrosis latens).
• Stages D and F: A small defect may resolve when it reaches the advancing ossification front.
• Stage E: Larger defects are unable to resolve, resulting in a cone of necrotic cartilage, which the ossification front advances around (osteochondrosis manifesta).
• Stage G: These lesions may be surrounded by bone as the ossification front advances.
• Stage H: Overlying cartilage can rupture or detach, causing osteochondrosis dissecans.

Some Arthritic Diseases

• Rheumatoid Arthritis: An autoimmune disease targeting joints and other organs (e.g., heart, lungs).
• Septic Arthritis: Infection in a joint causing inflammation.
• Psoriatic Arthritis: A consequence of psoriasis, an autoimmune disease causing red, scaly skin patches.
• Ankylosing Spondylitis: Autoimmune inflammation of the joints between vertebrae.
• Juvenile Idiopathic Arthritis: Autoimmune arthritis of unknown cause in under 16s.
• Gout: Build-up of uric acid in joints (often big toe), leading to inflammation.
• Osteoarthritis: Progressive breakdown of articular cartilage.

Symptoms/Consequences

• Pain
• Swelling
• Redness
• Warmth
• Stiffness/Immobility/Decreased range of motion (ROM)
• Limping/Lameness
• Abnormal posture
• Reduced activity
• Muscle atrophy
• Change in temperament

Assessing Pain (Pigs)

• Numerical Rating Scale (NRS): Pain scoring system using vocalizations (e.g., low volume, screams).
• Visual Analogue Scale (VAS): Pain scoring system using visual scales.
• Simple Descriptive Scale: Pain scoring system using descriptive words (e.g., normal, mild, moderate, severe) based on animal's behavior.

Assessing Lameness

• Varus malalignment: (o-shaped or bow-legged) - dysfunction in the medial joint aspect.
• Valgus malalignment: (x-shaped or cow-hocked) - dysfunction in the lateral joint aspect.
• Conformational changes in hind feet positioning under abdomen (standing under) or behind the stifle (standing back) indicate stifle and hock problems.

Osteoarthritis

• Highest prevalence of all arthritic diseases.
• Typically affects weight-bearing joints (e.g., dogs: elbow, hip, stifle, shoulder, back).
• Degradation of the joint can begin long before symptoms appear.
• No cure or reversal of the disease.
• Risk factors include age, gender, prior joint trauma, obesity, and sedentary lifestyle.

Structure of Synovial Joint

• Subchondral bone on either side of the joint (e.g., femur and tibia in diarthroidal stifle/knee joint).
• Bones capped with hyaline cartilage.
• Fibrocartilage menisci.
• Outer fibrous membrane (collagen) of the joint capsule.
• Inner synovial membrane (synovium).
• Synovial fluid
• Ligaments.
• Bursae.

Pathology of OA

• Degeneration of cartilage ECM and cartilage thinning - can lead to full thickness erosion exposing subchondral bone.
• Subchondral bone undergoes remodeling and sclerosis.
• Osteophyte formation.
• Synovial inflammation.

OA Initiation

• Recent studies suggest an inflammatory mechanism in initial stages of OA in response to mechanical injury.
• Trigger chondrocytes, osteoblasts, and synoviocytes to release cytokines (e.g., IL-1, IL-4, IL-9, IL-13, TNFα), and degradative enzymes (e.g., ADAMTS, MMPs).

OA Mechanisms

• (Diagram of healthy and OA affected cartilage showing various cellular components, markers, etc).

Cartilage Degeneration

• Healthy cartilage chondrocytes have low metabolic activity.
• Maintain anabolic/catabolic equilibrium supporting healthy ECM.
• Biomechanical changes upregulate synthetic activities for ECM repair.
• Early-stage OA attempts ECM repair from cell cloning, clusters, and hypertrophy - this leads to inability to form cartilage matrix.
• Disruption of cartilage results in increased inflammatory cytokines (e.g., IL-1B, IL-6, TNFα) and protease release (e.g., ADAMTS-4, ADAMTS-5, MMP-13).
• This alters ECM, particularly type II collagen organization → cartilage degradation and thinning, loss of elasticity, fibrillation/fissures.
• Age-related changes and oxidative stress lead to chondrocytes death/apoptosis - this results in cartilage loss.

Abnormal Bone Remodelling (stages)

• Subchondral bone undergoes abnormal remodeling. Early OA increases osteoclast activity, causing subchondral bone loss.
• Channels extend from subchondral bone into articular cartilage.
• Vascular invasion (angiogenesis) into the channels due to the growth factor VEGF.
• Extensions of sympathetic/sensory nerves from subchondral bone.
• Late OA remodeling is dominated by osteoblast activity.

Synovial Membrane

• The synovial membrane (synovium) produces synovial fluid (lubricin and hyaluronic acid).
• Lubricates the joint and nourishes articular cartilage.
• Composed of two cell types:
  • Fibroblasts - produce synovial components.
  • Macrophages - usually dormant but active during inflammation .

Synovitis

• OA causes joint swelling due to synovial fluid effusion (excess production) and thickening of synovium due to the hyperplasia of the intima layer.
• Cartilage breakdown fragments in synovial fluid contact the synovium → inflammatory response intended for repair but leads to chondrocyte dysfunction and further cartilage degradation.
• Inflammation increased production of cytokines and proteases (e.g., MMPs, and aggrecanases) in synovial cells and chondrocytes.
• Inflammation leads to synovial angiogenesis and increased synovial macrophages.
• Synovial membrane gradually becomes fibrotic over time.

Macroscopic Scoring of OA

• Grade 0: Normal cartilage - smooth, unbroken, homogenous white/off-white.
• Grade 1: Swelling/softening of cartilage; little brown homogenization.
• Grade 2: Superficial fibrillation - lightly broken surface and white/off-white to light brown.
• Grade 3: Deep fibrillation - coarsely broken surfaces, dark brown/grey/red.
• Grade 4: Subchondral bone exposure - stifled white and dark brown/red.

OARSI Histological Scoring of OA (grades 0-6)

• Numerical grading scale for cartilage damage based on microscopic appearance.

Grade 0 histological image

• Normal articular cartilage - smooth surface, with matrix and chondrocytes organized into superficial, middle, and deep zones.

Grade 1 histological image

• Uneven articular surface.
• Superficial fibrillation may be present.
• Cell death or proliferation may accompany superficial fibrillation.
• Mid and deep zones are unaffected.

Grade 2 histological image

• Focally fibrillation extends through the superficial to mid-zone portion.
• May be accompanied by increased cell proliferation, changes in matrix staining, or cell death in the mid zone.

Grade 3 histological image

• Matrix (cartilage) fibrillation extends downward into the mid zone.
• Fissures may branch and extend into the deep zone.
• Cell death and proliferation may be pronounced adjacent to fissures.

Grade 4 histological image

• Cartilage matrix loss - delamination in superficial cartilage is observed in early stage.
• More extensive erosion resulting in excavated loss of matrix in fissured areas.

Grade 5 histological image

• The unmineralized hyaline cartilage is eroded.
• Articular surface is mineralized cartilage or bone.
• Microfractures through the bone plate may occur.
• Reparative fibrocartilage may occupy gaps in the surface.

Grade 6 histological image

• Processes of microfractures, repair, and bone remodeling change the articular surface contour.
• Fibrocartilage grown along previously eroded/denuded surface.
• Marginal and central osteophytes form.
• Extensive articular contour deformation.

Management/Treatment

• Weight management/control/maintenance.
• Regular, moderate, controlled physical activity.
• Joint supplements/neutraceuticals: e.g., omega-3 fatty acids, glucosamine/chondroitin sulphate, polysulfated glycosaminoglycans (GAGs) - injection.
• Analgesics/anti-inflammatories: e.g., NSAIDs, opioids (e.g., tramadol), steroids (for some types of arthritis).
• Disease-modifying anti-rheumatic drugs (DMARDs): e.g., hydroxychloroquine, methotrexate (for specific types of arthritis).
• Surgery.
• Alternative treatments: e.g., low-level laser treatment, acupuncture, hydrotherapy, shockwave treatment, stem cell therapy.

Some Further Reading

• Key articles/publications cited in the presentation.

Test your knowledge on osteoarthritis and osteochondrosis with this quiz. Assess your understanding of the pathological processes, symptoms, and risk factors associated with these arthritic diseases, as well as the scoring methods used to evaluate cartilage damage in animals.