Glucocorticoid induced osteopenia in cancellous bone of sheep: validation of large animal model for spine fusion and biomaterial research.
METHODS
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.


BACKGROUND
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.


CONCLUSIONS
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.
Ding
Ming
M
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
Cheng
Liming
L
Bollen
Peter
P
Schwarz
Peter
P
Overgaard
Søren
S
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001672:Biocompatible Materials; D015415:Biomarkers / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000601:surgery; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000601:surgery; D002118:Calcium / Q000172:deficiency; D002136:Calcium, Dietary; D003094:Collagen / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects; D005938:Glucocorticoids; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000601:surgery; D008422:Materials Testing / Q000379:methods*; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010758:Phosphorus / Q000172:deficiency; D016226:Phosphorus, Dietary; D011239:Prednisolone; D013123:Spinal Fusion / Q000295:instrumentation*; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects; D013997:Time Factors; D055114:X-Ray Microtomography
D001672:Biocompatible Materials; D015415:Biomarkers; D002136:Calcium, Dietary; D005938:Glucocorticoids; D010446:Peptide Fragments; D016226:Phosphorus, Dietary; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D015675:Osteocalcin; D010758:Phosphorus; D003094:Collagen; D011239:Prednisolone; D000469:Alkaline Phosphatase; D002118:Calcium