title: Validation of the sheep as a large animal model for the study of vertebral osteoporosis.
abstract: Rats have long been the animal of choice for research in the field of osteoporosis. In the search for a complementary large animal model the sheep appears useful but hitherto the extent of bone loss from the spine has failed to reach a level that is generally accepted as osteoporotic in humans. Osteoporosis was induced in ten sheep using ovariectomy, low calcium diet and steroid injection for 6 months. Bone samples of iliac crest (IC), lumbar spine (LS), and proximal femur (PF) from the osteoporotic sheep were compared with those from four normal sheep using densitometry, histomorphometry, biochemistry and basic mechanical testing. The differences were examined using an analysis of variance with Tukey-Kramer test. Overall, the bone mineral density at LS and PF decreased more than 25% after treatment. Trabecular bone volume decreased by 29.2, 33.4 and 42.6% in IC, LS and PF, respectively. The failure load of the LS in axial compression was reduced to 2,003 from 6,140 N. The extent of bone loss was sufficient to categorise these sheep as osteoporotic although the pattern of bone loss varied between sites. Reduced mechanical competence in LS confirmed the suitability of this model for evaluation of potential treatments for osteoporosis.
authors.affiliation: The Adelaide Centre for Spinal Research, Institute of Medical and Veterinary Science, PO Box 14, Rundle Mall, Adelaide, SA 5000, Australia. reza.zarrinkalam@imvs.sa.gov.au
authors.forename: M R
authors.initials: MR
authors.lastname: Zarrinkalam
authors.forename: H
authors.initials: H
authors.lastname: Beard
authors.forename: C G
authors.initials: CG
authors.lastname: Schultz
authors.forename: R J
authors.initials: RJ
authors.lastname: Moore
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity; D001696:Biomechanical Phenomena; D015519:Bone Density; D024042:Collagen Type I / Q000097:blood; D019245:Compressive Strength; D003907:Dexamethasone / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000473:pathology; D008159:Lumbar Vertebrae / Q000473:pathology*; D010024:Osteoporosis / Q000209:etiology / Q000473:pathology*; D010052:Ovariectomy; D010455:Peptides / Q000097:blood; D012756:Sheep
chemical_list: D018931:Antineoplastic Agents, Hormonal; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003907:Dexamethasone