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.
Bibliographical noteFunding Information:
We thank Ben Kriederman (Histotox), Brian Omura (BolderBioPATH), Connie Kilwinski (Centocor), Julio Tejada (Pfizer), Margaret McNulty (Carlson laboratory), Nicole Schmitz (Aigner laboratory), Phil Bendele (BolderBioPATH), and Steve Settle (Pfizer) for participating in the reliability study. No external sources of funding were provided for this work except that the printing costs were supported by an unrestricted educational grant to OARSI by Bayer, Expanscience, Genzyme, Lilly, MerckSerono, Novartis, Pfizer, SanofiAventis, and Servier. The work performed was not influenced at any stage by the support provided.