MECHANICAL ARTHROPATHY: CARTILAGE PATHOPHYSIOLOGY AND OSTEOARTHRITIS

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MECHANICAL ARTHROPATHYCARTILAGE PATHOPHYSIOLOGY
AND OSTEOARTHRITIS

• Grant W. Cannon, M.D.
• Friday, November 18, 2005

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OsteoarthritisTerminology

• Osteoarthritis
• Osteoarthrosis
• Degenerative Joint Disease
• Hypertrophic Arthropathy

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OsteoarthritisDefinition

• Progressive disintegration of articular cartilage
• Formation of new bone in the floor of the
  cartilage lesions (eburnation) and at the joint
  margins (osteophtyes)

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OsteoarthritisNormal Cartilage Review

• Nutrition
• Chondrocytes
• Collagen
• Proteoglycans
• Hyaluronic Acid

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Normal Cartilage ReviewComponents

• Water - 65-80 of cartilage is water
• Major matrix components- 90 of dry weight
• Proteoglycans (particularly aggrecan)
• Collagen
• Chondrocytes 1-2 of volume
• Other important components
• Enzymes - E.g. Matrix metaloproteinases (MMPs) -
  e.g. collagenase
• Enzyme inhibitors. E.g. Tissue inhibitors of
  metaloproteinases (TIMP)

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Normal Cartilage ReviewChondrocytes

• Chondrocytes 1-2 of volume
• Biosynthetically active, but relatively quiescent
• Produce proteoglycans, but little collagen
• Source of enzymes and enzyme inhibitors

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Normal Cartilage ReviewCollagen

• Types of collagen
• Type II in hyaline cartilage
• Type II and Type I in fibrocartilage
• Vertical orientation in deep regions
• Horizontal orientation in superficial regions

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Normal Cartilage ReviewProteoglycans - I

• Properties
• Hydrophilic
• Polar
• Components
• Glycosaminoglycans
• Core protein - binds GAGs to make proteoglycans
• Hyaluronic Acid - Non-covalent binding

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Normal Cartilage ReviewProteoglycans -
Components

• Glycosaminoglycans (GAGs) - "acid
  mucopolysaccharides
• Chondroitins
• Heparins
• Keratan sulfates
• Core protein - binds GAGs to make proteoglycans
• Hyaluronic Acid - Non-covalent binding
• Most common cartilage proteoglycan is aggrecan

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OsteoarthritisNormal Cartilage Review

• Nutrition
• Chondrocytes
• Collagen
• Proteoglycans
• Hyaluronic Acid

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Pathology of Osteoarthritis

• Gross Pathology
• Biochemical Abnormalities

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Pathology of OsteoarthritisGross Pathology

• Fibrillation and flaking of the cartilage surface
• Loss of cartilage
• Subchondral sclerosis (Eburnation)
• Osteophyte formation

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Pathology of OsteoarthritisGross Pathology

• Fibrillation and flaking of the cartilage surface
• Loss of cartilage
• Subchondral sclerosis (Eburnation)
• Osteophyte formation

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Pathology of OsteoarthritisBiochemical
Abnormalities

• Increase in water content
• Change in proteoglycans (PGs)
• Collagen
• Chondrocyte - damage and loss of chondrocytes is
  a late finding in OA
• Possible role of inflammation.

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Pathology of OsteoarthritisBiochemical
Abnormalities

• Change in proteoglycans (PGs)
• Increased turnover and degradation
• Decrease in PG aggregation (smaller PGs)
• Increase in extractable PGs
• Decrease in chondroitin sulfate length
• Change in GAG composition

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Pathology of OsteoarthritisBiochemical
Abnormalities

• Collagen
• Increase in collagen synthesis - a reflection of
  increased turnover
• Production of some type I collagen

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Pathology of OsteoarthritisBiochemical
Abnormalities

• Chondrocyte - damage and loss of chondrocytes is
  a late finding in OA
• Possible role of inflammation
• Increase in cytokine levels (IL-1 and TNF-")
• Unclear what represent the primary process

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Pathology of OsteoarthritisBiochemical
Abnormalities
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Pathology of OsteoarthritisBiochemical
Abnormalities
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Pathology of Osteoarthritis

• Gross Pathology
• Biochemical Abnormalities

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OsteoarthritisRisk Factors
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OsteoarthritisRisk Factors

• Increasing age
• Women
• Obesity
• Trauma (Heavy exercise on a normal joint has not
  generally not been associated with increased OA)
• Inherited genetic mutations of collagen
• Other causes of joint injury (e.g. inflammatory
  arthritis, congenital dislocations, etc)

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OsteoarthritisClinical Manifestation

• Symptoms
• Physical Finding
• Laboratory

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Clinical ManifestationSymptoms

• Mechanical joint pain
• "Jelling" sensation
• Absence of morning stiffness

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Clinical ManifestationPhysical Finding

• Local tenderness
• Bony swelling
• Crepitus

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Clinical ManifestationLaboratory

• Synovial Effusion - non-inflammatory
  (lt2,000 WBCs/mm3)
• Other test normal

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OsteoarthritisJoint Distribution

• Large joints of the lower extremities (Hips and
  Knees)
• Distal interphalangeal joints (DIPs) - Heberdon's
  Nodes
• Proximal interphalangeal joints (PIPs) -
  Bouchard's Nodes
• Shoulder involvement is rare

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OsteoarthritisRadiographic Manifestations

• Joint space narrowing (cartilage loss)
• Subchondral sclerosis (Eburnation)
• Osteophyte formation
• Subchondral cysts

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OsteoarthritisRadiographic Manifestations

• Joint space narrowing (cartilage loss)
• Subchondral sclerosis (Eburnation)
• Osteophyte formation
• Subchondral cysts

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Osteoarthritis ClassificationPrimary

• Idiopathic
• Generalized osteoarthritis
• Erosive osteoarthritis

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Osteoarthritis ClassificationSecondary

• Congenital or developmental defects
• Post-traumatic
• Due to prior inflammatory joint disease
• Metabolic disorders
• Endocrinopathies
• Familial genetic disorders
• Neuropathic disorders/Charcot joints
• Miscellaneous

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Osteoarthritis Management

• Goals
• Non-medical therapy
• Medical therapy
• Joint injection
• Alternative therapies under investigation
• Surgery

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Osteoarthritis ManagementGoals

• Pain relief
• Minimize disability
• Stopping or delaying the destructive process

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Osteoarthritis ManagementNon-Medical Therapy

• Weight reduction
• Physical therapy
• Maintenance of muscle function
• Maintenance of range of motion
• Avoid weight bearing exercises (e.g. jogging)
• Appliances (bathtub bars, crutches, walkers,
  elevated toilet seat, etc.)

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Osteoarthritis ManagementMedical Therapy

• Non-narcotic analgesia (e.g. acetaminophen)
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Specific COX-2 inhibitors

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Osteoarthritis ManagementJoint Injection

• Corticosteroids
• Hyaluronate preparations

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Osteoarthritis ManagementAlternative Therapies

• Chondroitin sulfate
• Glucosamine
• Recent data
• No benefit over placebo in most patients
• No adverse events

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Osteoarthritis ManagementSurgery

• Osteotomy
• Total joint replacement
• Joint fusion

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Diffuse IdiopathicSkeletal Hyperostosis

• Nomenclature
• DISH
• Forrestier's Disease
• Characteristics
• Variable clinical symptoms
• No specific treatment program

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Diffuse IdiopathicSkeletal Hyperostosis

• Characteristics
• Calcification of the anterior spinal ligament
• Flowing osteophytes
• Involvement of at least four contiguous vertebral
  bodies
• Sparing of posterior elements
• Maintenance of disc height

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Normal Cervical Spine
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Diffuse IdiopathicSkeletal Hyperostosis

• Nomenclature
• Characteristics
• Variable clinical symptoms - often asymptotic
• No specific treatment program

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Osteochondritis Dessicans

• Clinical Features
• Articular cartilage and underlying bone loose in
  the joint.
• Frequently associated with minor trauma
• Often a familial tendency
• Often seen in young adults

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Osteochondritis Dessicans

• Management
• Surgical Repair
• Some cases may be observed and fragments removed

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Chondromalacia Patellae

• Clinical Characteristics
• Thinning and damage of cartilage of
  patellofemoral joint
• More common in women
• May be associated with subluxation

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Chondromalacia Patellae

• Management
• Quadriceps muscle strengthening exercises
• Patellar taping
• Non steroidal anti-inflammatory drugs (NSAIDs)
• Surgery
• Lateral release
• Avoid major surgery (e.g. patellectomy)

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Neuropathic Arthritis

• Clinical Features
• Diseases associated with Neuropathic arthritis
• Management

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Neuropathic ArthritisClinical features

• Sensory neurologic deficit
• Joint deformity and destruction out of proportion
  to the severity of pain.
• Painless in the face of marked deformity
• Less painful than expected in view of the degree
  of deformity.
• Characteristically, there is significant
• Hypertrophic bone formation,
• Subchondral sclerosis,
• Severe cartilage degeneration
• Loose bone fragments.

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Neuropathic ArthritisDiseases Associated with
Neuropathic Arthritis

• Diabetes mellitus
• Syringomyelia
• Syphilis with tabes dorsalis
• Any peripheral neuropathy

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Neuropathic ArthritisManagement

• Education
• Reduce joint trauma
• DO NOT replace with artificial joints

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Osteonecrosis(Avascular Necrosis/Aseptic
necrosis)

• Pathophysiology
• Diseases associated with osteonecrosis
• Clinical Stages - In all stages joint space
  (cartilage) is maintained.
• Diagnosis
• Management

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OsteonecrosisPathophysiology

• Compromise of the blood supply to bone
• May in some cases be the result of increase in
  marrow fat and an increase in pressure within the
  bone
• May involve many sites - Hip is the most common
  site

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OsteonecrosisDiseases associated with
osteonecrosis

• Corticosteroids
• Glucocorticoid treatment (e.g. prednisone)
• Cushings disease
• Trauma
• Inflammatory arthritis
• Systematic lupus erythematosus
• Rheumatoid arthritis
• Hematologic disorders
• Hypercoagulability (antiphospholipid syndrome)
• Hemoglobinophathies (e.g. Sickle cell disease)
  
  
  
  
• 
  

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OsteonecrosisDiseases associated with
osteonecrosis

• Infiltrative disorders
• Gauchers disease
• Decompression sickness (e.g. deep sea divers)
• Alcoholism
• Cirrhosis
• Malignancies
• Idiopathic

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OsteonecrosisClinical Stages

• Stage 0 - No symptoms, normal radiographs,
  abnormal MRI
• Stage 1 - Symptoms, normal radiographs, abnormal
  MRI
• Stage 2 - Patchy mottled sclerosis
• Stage 3 - Early bone collapse - Subcortical band
  immediately under the articular cartilage
  (crescent sign)
• Stage 4 - Late bone collapse - flattening of
  femoral head

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OsteonecrosisDiagnosis

• Plan radiographs
• Magnetic Resonance Imaging (MRI) - EARLY
• Bone Scans
• May initially appear "cold" (decrease uptake)
  showing decreased blood flow.
• Later the affected area may appear "not'
  (increased uptake) showing revascularization and
  appositional new bone formation.
• Bone marrow pressure measurement and venography
• Bone biopsy

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OsteonecrosisManagement

• No proven effective treatment
• Some preliminary results with early lesions
• Vascular bone grafts
• Core decompression
• Surgery with joint replacement in advanced
  cases.

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MECHANICAL ARTHROPATHYCARTILAGE PATHOPHYSIOLOGY
AND OSTEOARTHRITIS

• Questions?