Osteoarthritis

Osteoarthritis (OA)

Clinical Background

Arthritis is the leading cause of disability in the United States causing at least 9,500 deaths, 750,000 hospitalizations and 36 million ambulatory care visits annually within the United States. Approximately 80% of all arthritis is osteoarthritis.  The causes of arthritis are still largely unknown. Osteoarthritis (OA) is thought to be caused primarily by injury to the joint cartilage, whether through trauma or through wear and tear in old age or due to overuse.   Current treatment for OA primarily consists of non-steroidal anti-inflammatory compounds (NSAIDs).

Animal Model

Biomodels has developed a model of osteoarthritis in rats, in which the ACL and MCL of the left knee are surgically transected without damaging the meniscus.  The wound is closed and the animal is allowed to move freely.  Osteoarthritis develops over a period of 4-5 weeks and can be successfully treated with intra-articular injections of anti-inflammatories.  Systemic treatments have not yet been evaluated in this model.  End points are predominantly histological, with scores based on the OARSI modified Mankin Scale, a 17 point scale that evaluated the articular cartilage structures,  proteoglycan loss and cellularity.  Specific histological stains to evaluate articular cartilage such as Safonin O and Toluidine blue can be used, as can immunhistochemistry to evaluate the levels of specific cartilage associated proteins.  X-rays may also be taken.

OARSI Modified Mankin Score

Parameter

Grade

Description

Articular

Cartilage

Structures

0

Normal, smooth uninterrupted, surface

1

Mild Surface irregularities

2

Irregular surface, 1-3 superficial clefts_

3

>3 clefts and/or loss of cartilage in the superficial zone

4

1-3 clefts extending into the middle zone

5

>3 clefts and/or loss of cartilage extending into the middle zone

6

1-3 clefts extending into the deep zone

7

>3 clefts extending in to the deep zone and/or loss of cartilage to deep zone

8

Clefts or loss of cartilage extending to the zone of calcified cartilage

Proteoglycan Loss

(toluidine blue staining)               

0

Uniform staining throughout articular cartilage

1

Loss of staining in superficial zone only and for < half length of the condyle or plateau

2

Loss of staining in superficial zone for half the length or greater of the condyle or plateau

3

Loss of staining in superficial and middle zone for < half the length  of the condyle or plateau

4

Loss of staining in superficial and middle zones for half the length or greater of the condyle or plateau

5

Loss of staining in all 3 zones for <half the length of the condyle or plateau

6

Loss of staining in all 3 zones for half the length or greater of the condyle or plateau

Cellularity

0

Normal (1/2 cells/lacuna)

1

Diffuse/slight hypercellularity

2

regions of hypercellularity and cloning

3

Hypocellularity