TY - JOUR

T1 - Glucocorticoid induced osteopenia in cancellous bone of sheep: validation of large animal model for spine fusion and biomaterial research

AU - Ding, Ming

AU - Cheng, Liming

AU - Bollen, Peter

AU - Schwarz, Peter

AU - Overgaard, Søren

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1097/BRS.0b013e3181b8e0ff

DO - 10.1097/BRS.0b013e3181b8e0ff

M3 - Journal article

C2 - 20110841

VL - 35

SP - 363

EP - 370

JO - Spine

JF - Spine

SN - 0362-2436

IS - 4

ER -