title: A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare.
abstract: Animal models are necessary to evaluate new options for the treatment of fractures in osteoporotic bone. They permit both the biological response of a living system and the influence of the pathological processes to be taken into account. A sheep model for osteoporosis was established by combining oestrogen deficiency, calcium and vitamin D-deficient diet with steroid medication. Bone mineral density (BMD) was reduced by >30% after 12 weeks of combined treatment. Osteoporosis similar to the human situation with corresponding changes in the micro-architecture and mechanical properties of bone was observed. This publication focuses on the impressive results obtained with the model and contrasts them with considerations of animal welfare. Considerable side-effects associated with steroid medication became manifest. Animals in the treatment groups showed signs of infection of various degrees due to the immunosuppressive effect of the medication. The infections were mostly caused by Corynebacterium pseudotuberculosis. Antibody testing revealed a 100% prevalence of infection in this breed of sheep. A modification of the steroid treatment, i.e. less-frequent injections, reduced the incidence of side-effects. This sheep model shows a significant and reproducible reduction in cancellous BMD of >30%, including relevant changes in biomechanical properties and increased fracture risk. However, the severity of the side-effects cannot be overlooked. The model must be improved if it is to be used in the future. Options to reduce the side-effects are discussed.
authors.affiliation: AO Research Institute, Clavadelerstrasse, CH-7270 Davos Platz, Switzerland. marcus.egermann@aofoundation.org
authors.forename: M
authors.initials: M
authors.lastname: Egermann
authors.forename: J
authors.initials: J
authors.lastname: Goldhahn
authors.forename: R
authors.initials: R
authors.lastname: Holz
authors.forename: E
authors.initials: E
authors.lastname: Schneider
authors.forename: C A
authors.initials: CA
authors.lastname: Lill
mesh_terms: D000827:Animal Welfare; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D017102:Fracture Healing / Q000502:physiology; D005598:Fractures, Spontaneous / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D010024:Osteoporosis / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D010865:Pilot Projects; D012756:Sheep; D013256:Steroids / Q000008:administration & dosage; D013977:Tibia / Q000503:physiopathology
chemical_list: D013256:Steroids