The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat.
OBJECTIVE
During the development of disease-modifying osteoarthritis (OA) drugs, rat models of OA are frequently used for a first assessment of in vivo efficacy. The most efficacious compound in the rat model may then be tested in a larger animal model before entering human trials. The aim of this study was to describe a histologic scoring system for use in different models of OA in rats that allows standardization and comparison of results obtained by different investigators.


METHODS
The experience of the authors with current scoring systems and the range of lesions observed in rat and human OA studies were considered in recommending this common paradigm for rat histologic scoring. Considerations were made for reproducibility and ease of use for new scorers. Additional scoring paradigms may be employed to further identify specific effects of some disease-modifying drugs.


RESULTS
Although the described scoring system is more complex than the modified Mankin scores, which are recommended for some other species, the reliability study showed that it is easily understood and can be reproducibly used, even by inexperienced scorers.


CONCLUSIONS
The scoring paradigm described here has been found to be sufficiently sensitive to discriminate between treatments and to have high reproducibility. Therefore we recommend its use for evaluation of different rat OA models as well as assessment of disease-modifying effects of treatments in these models.
Gerwin
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Novartis Institutes for BioMedical Research, Musculoskeletal Disease Area, 4002 Basel, Switzerland. nicole.gerwin@novartis.com
Bendele
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Glasson
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Carlson
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D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007596:Joints / Q000473:pathology; D015588:Observer Variation; D010003:Osteoarthritis / Q000473:pathology*; D051381:Rats; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000473:pathology