Ming Ding1, Liming Cheng, Peter Bollen, Peter Schwarz, Søren Overgaard. 1. Orthopaedic Research Laboratory, Department of Orthopaedics O, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark. ming.ding@ouh.regionsyddanmark.dk
Abstract
STUDY DESIGN: Glucocorticoid with low calcium and phosphorus intake induces osteopenia in cancellous bone of sheep. OBJECTIVE: To validate a large animal model for spine fusion and biomaterial research. SUMMARY OF BACKGROUND DATA: A variety of ovariectomized animals has been used to study osteoporosis. Most experimental spine fusions were based on normal animals, and there is a great need for suitable large animal models with adequate bone size that closely resemble osteoporosis in humans. METHODS: Eighteen female skeletal mature sheep were randomly allocated into 3 groups, 6 each. Group 1 (GC-1) received prednisolone (GC) treatment (0.60 mg/kg/day, 5 times weekly) for 7 months. Group 2 (GC-2) received the same treatment as GC-1 for 7 months followed by 3 months without treatment. Group 3 was left untreated and served as the controls. All sheep received restricted diet with low calcium and phosphorus during experiment. After killing the animals, cancellous bone specimens from the vertebra, femurs, and tibias were micro-CT scanned and tested mechanically. Serum biomarkers were determined. RESULTS: In lumbar vertebra, the GC treatment resulted in significant decrease of cancellous bone volume fraction and trabecular thickness, and bone strength. However, the microarchitecture and bone strength of GC-2 recovered to a similar level of the controls. A similar trend of microarchitectural changes was also observed in the distal femur and proximal tibia of both GC treated sheep. The bone formation marker serum-osteocalcin was largely reduced in GC-1 compared to the controls, but recovered with a rebound increase at month 10 in GC-2. CONCLUSION: The current investigation demonstrates that the changes in microarchitecture and mechanical properties were comparable with those observed in humans after long-term GC treatment. A prolonged GC treatment is needed for a long-term observation to keep osteopenic bone. This model resembles long-term glucocorticoid treated osteoporotic model, and is useful in preclinical studies.
STUDY DESIGN: Glucocorticoid with low calcium and phosphorus intake induces osteopenia in cancellous bone of sheep. OBJECTIVE: To validate a large animal model for spine fusion and biomaterial research. SUMMARY OF BACKGROUND DATA: A variety of ovariectomized animals has been used to study osteoporosis. Most experimental spine fusions were based on normal animals, and there is a great need for suitable large animal models with adequate bone size that closely resemble osteoporosis in humans. METHODS: Eighteen female skeletal mature sheep were randomly allocated into 3 groups, 6 each. Group 1 (GC-1) received prednisolone (GC) treatment (0.60 mg/kg/day, 5 times weekly) for 7 months. Group 2 (GC-2) received the same treatment as GC-1 for 7 months followed by 3 months without treatment. Group 3 was left untreated and served as the controls. All sheep received restricted diet with low calcium and phosphorus during experiment. After killing the animals, cancellous bone specimens from the vertebra, femurs, and tibias were micro-CT scanned and tested mechanically. Serum biomarkers were determined. RESULTS: In lumbar vertebra, the GC treatment resulted in significant decrease of cancellous bone volume fraction and trabecular thickness, and bone strength. However, the microarchitecture and bone strength of GC-2 recovered to a similar level of the controls. A similar trend of microarchitectural changes was also observed in the distal femur and proximal tibia of both GC treated sheep. The bone formation marker serum-osteocalcin was largely reduced in GC-1 compared to the controls, but recovered with a rebound increase at month 10 in GC-2. CONCLUSION: The current investigation demonstrates that the changes in microarchitecture and mechanical properties were comparable with those observed in humans after long-term GC treatment. A prolonged GC treatment is needed for a long-term observation to keep osteopenic bone. This model resembles long-term glucocorticoid treated osteoporotic model, and is useful in preclinical studies.
Authors: Isabel R Dias; José A Camassa; João A Bordelo; Pedro S Babo; Carlos A Viegas; Nuno Dourado; Rui L Reis; Manuela E Gomes Journal: Curr Osteoporos Rep Date: 2018-04 Impact factor: 5.096
Authors: Tyler C Kreipke; Nicole C Rivera; Jacqueline G Garrison; Jeremiah T Easley; A Simon Turner; Glen L Niebur Journal: J Biomech Date: 2014-03-25 Impact factor: 2.712
Authors: Stefan Maenz; Olaf Brinkmann; Raimund W Kinne; Matthias Bungartz; Ines Hasenbein; Christina Braun; Elke Kunisch; Victoria Horbert; Francesca Gunnella; André Sachse; Sabine Bischoff; Harald Schubert; Klaus D Jandt; Jörg Bossert; Dominik Driesch Journal: J Bone Miner Metab Date: 2020-04-15 Impact factor: 2.626
Authors: Christian Heiss; Stefanie Kern; Deeksha Malhan; Wolfgang Böcker; Markus Engelhardt; Diaa Eldin S Daghma; Sabine Stoetzel; Jakob Schmitt; Matthias Ivo; Vivien Kauschke; Katrin S Lips; Kamen Tushtev; Kurosch Rezwan; Thaqif El Khassawna Journal: Med Sci Monit Basic Res Date: 2017-10-02