1. MECHANICAL ARTHROPATHY: CARTILAGE PATHOPHYSIOLOGY AND OSTEOARTHRITIS
Grant W. Cannon, M.D.
Friday, November 18, 2005

2. Osteoarthritis Terminology
Osteoarthrosis
Degenerative Joint Disease
Hypertrophic Arthropathy

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

5. Osteoarthritis Normal Cartilage Review
Nutrition
Chondrocytes
Collagen
Proteoglycans
Hyaluronic Acid

7. Normal Cartilage Review Components
Water % 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)

8. Normal Cartilage Review Chondrocytes
Chondrocytes 1-2% of volume
Biosynthetically active, but relatively quiescent
Produce proteoglycans, but little collagen
Source of enzymes and enzyme inhibitors

9. Normal Cartilage Review Collagen
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

11. Normal Cartilage Review Proteoglycans - I
Properties
Hydrophilic
Polar
Components
Glycosaminoglycans
Core protein - binds GAGs to make proteoglycans
Hyaluronic Acid - Non-covalent binding

13. Normal Cartilage Review Proteoglycans - 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

14. Osteoarthritis Normal Cartilage Review
Nutrition
Chondrocytes
Collagen
Proteoglycans
Hyaluronic Acid

15. Pathology of Osteoarthritis
Gross Pathology
Biochemical Abnormalities

16. Pathology of Osteoarthritis Gross Pathology
Fibrillation and flaking of the cartilage surface
Loss of cartilage
Subchondral sclerosis (Eburnation)
Osteophyte formation

23. Pathology of Osteoarthritis Gross Pathology
Fibrillation and flaking of the cartilage surface
Loss of cartilage
Subchondral sclerosis (Eburnation)
Osteophyte formation

24. Pathology of Osteoarthritis Biochemical 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.

25. Pathology of Osteoarthritis Biochemical 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

27. Pathology of Osteoarthritis Biochemical Abnormalities
Collagen
Increase in collagen synthesis - a reflection of increased turnover
Production of some type I collagen

28. Pathology of Osteoarthritis Biochemical 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

29. Pathology of Osteoarthritis Biochemical Abnormalities

30. Pathology of Osteoarthritis Biochemical Abnormalities

31. Pathology of Osteoarthritis
Gross Pathology
Biochemical Abnormalities

32. Osteoarthritis Risk Factors

33. Osteoarthritis Risk 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)

35. Osteoarthritis Clinical Manifestation
Symptoms
Physical Finding
Laboratory

36. Clinical Manifestation Symptoms
Mechanical joint pain
"Jelling" sensation
Absence of morning stiffness

37. Clinical Manifestation Physical Finding
Local tenderness
Bony swelling
Crepitus

38. Clinical Manifestation Laboratory
Synovial Effusion - non-inflammatory (<2,000 WBCs/mm3)
Other test normal

39. Osteoarthritis Joint 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

42. Osteoarthritis Radiographic Manifestations
Joint space narrowing (cartilage loss)
Subchondral sclerosis (Eburnation)
Osteophyte formation
Subchondral cysts

50. Osteoarthritis Radiographic Manifestations
Joint space narrowing (cartilage loss)
Subchondral sclerosis (Eburnation)
Osteophyte formation
Subchondral cysts

51. Osteoarthritis Classification Primary
Idiopathic
Generalized osteoarthritis
Erosive osteoarthritis

52. Osteoarthritis Classification Secondary
Congenital or developmental defects
Post-traumatic
Due to prior inflammatory joint disease
Metabolic disorders
Endocrinopathies
Familial genetic disorders
Neuropathic disorders/Charcot joints
Miscellaneous

53. Osteoarthritis: Management
Goals
Non-medical therapy
Medical therapy
Joint injection
Alternative therapies under investigation
Surgery

54. Osteoarthritis: Management Goals
Pain relief
Minimize disability
Stopping or delaying the destructive process

55. Osteoarthritis: Management Non-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.)

56. Osteoarthritis: Management Medical Therapy
Non-narcotic analgesia (e.g. acetaminophen)
Non-steroidal anti-inflammatory drugs (NSAIDs)
Specific COX-2 inhibitors

57. Osteoarthritis: Management Joint Injection
Corticosteroids
Hyaluronate preparations

58. Osteoarthritis: Management Alternative Therapies
Chondroitin sulfate
Glucosamine
Recent data
No benefit over placebo in most patients
No adverse events

59. Osteoarthritis: Management Surgery
Osteotomy
Total joint replacement
Joint fusion

62. Diffuse Idiopathic Skeletal Hyperostosis
Nomenclature
DISH
Forrestier's Disease
Characteristics
Variable clinical symptoms
No specific treatment program

63. Diffuse Idiopathic Skeletal 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

64. Normal Cervical Spine

67. Diffuse Idiopathic Skeletal Hyperostosis
Nomenclature
Characteristics
Variable clinical symptoms - often asymptotic
No specific treatment program

68. 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

71. Osteochondritis Dessicans
Management
Surgical Repair
Some cases may be observed and fragments removed

72. Chondromalacia Patellae
Clinical Characteristics
Thinning and damage of cartilage of patellofemoral joint
More common in women
May be associated with subluxation

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

74. Neuropathic Arthritis
Clinical Features
Diseases associated with Neuropathic arthritis
Management

75. Neuropathic Arthritis Clinical 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.

79. Neuropathic Arthritis Diseases Associated with Neuropathic Arthritis
Diabetes mellitus
Syringomyelia
Syphilis with tabes dorsalis
Any peripheral neuropathy

80. Neuropathic Arthritis Management
Education
Reduce joint trauma
DO NOT replace with artificial joints

81. Osteonecrosis (Avascular Necrosis/Aseptic necrosis)
Pathophysiology
Diseases associated with osteonecrosis
Clinical Stages - In all stages joint space (cartilage) is maintained.
Diagnosis
Management

82. Osteonecrosis Pathophysiology
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

84. Osteonecrosis Diseases associated with osteonecrosis
Corticosteroids
Glucocorticoid treatment (e.g. prednisone)
Cushing’s disease
Trauma
Inflammatory arthritis
Systematic lupus erythematosus
Rheumatoid arthritis
Hematologic disorders
Hypercoagulability (antiphospholipid syndrome)
Hemoglobinophathies (e.g. Sickle cell disease)

85. Osteonecrosis Diseases associated with osteonecrosis
Infiltrative disorders
Gaucher’s disease
Decompression sickness (e.g. deep sea divers)
Alcoholism
Cirrhosis
Malignancies
Idiopathic

86. Osteonecrosis Clinical 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

87. Osteonecrosis Diagnosis
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

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

94. MECHANICAL ARTHROPATHY: CARTILAGE PATHOPHYSIOLOGY AND OSTEOARTHRITIS
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