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Periosteal Hyperostosis (Exostosis) in DBA/1 Male Mice

Immunex Corporation, 51 University Street, Seattle, Washington 98101, USA, schuhj{at}bainbridge.net

Randy Hall

Immunex Corporation, 51 University Street, Seattle, Washington 98101, USA

Dina Lambert

Immunex Corporation, 51 University Street, Seattle, Washington 98101, USA

Kim Harrington

Immunex Corporation, 51 University Street, Seattle, Washington 98101, USA

Ken Mohler

Immunex Corporation, 51 University Street, Seattle, Washington 98101, USA

Dauphine Barone

Immunex Corporation, 51 University Street, Seattle, Washington 98101, USA

Periosteal hyperostosis (exostosis) was identified in 5.9% (11/188) of DBA/1 male mice 10—14 weeks old used for collagen-induced arthritis (CIA) efficacy testing of immunomodulatory biologics. Mice with and without CIA in the affected limb, and also control and treated groups, were involved, with bilateral lesions in one mouse. Hyperostosis was characterized by circumferential and raised masses of variable location, length, and laterality, generally external to but occasionally breaching the periosteum of the metatarsals, metacarpals, tibia, femur, and humerus. Proportionally, the hyperostotic foci consisted of cancellous and woven bone, followed by osteoid, cartilage, and fibrous connective tissue and rarely infl ammatory cells. A displaced, presumably pathological fracture with callus formation was a concurrent lesion in only one case. Tartrate-resistant acid phosphatase-positive cells were frequent at bony interfaces, indicating an active resorptive process. Periosteal hyperostosi s is an incidental and potentially common finding in DBA/1 mice. Underreporting may occur due to the male bias in disease expression of this CIA model, sampling bias (generally paws only), tissue obliteration in the presence of CIA, and lack of comprehensive historical data on the background and aging lesions in this strain of mouse. Identification of such confounding bony lesions is important to the interpretation of efficacy studies, and suggests the need to further examine the biology of bone development in this strain of mouse.

Key Words: Animal model of human disease • efficacy study • murine collagen-induced arthritis • musculoskeletal pathology.

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