There is a great need for suitable large animal models that closely resemble osteoporosis in humans, and that they have adequate bone size for bone prosthesis and biomaterial research. This study aimed to investigate effects of a 7 month glucocorticoid (GC) treatment alone without ovariectomy on the properties of sheep cancellous bone.

Eighteen female sheep were randomly allocated into 3 groups: group 1 (GC-1) received GC (0.60mg/kg/day methylprednisolone) 5 days weekly for 7 months; group 2 (GC-2) received the same treatment regime for 7 months, and further observed for 3 months without GC; and group 3 served as the control group, and left untreated for 7 months. The sheep received restricted diet.

After 7 months of GC treatment. Cancellous bone volume fraction of the 5th lumbar vertebra in the GC-1 group was reduced by −35%, trabecular thickness by −28%, and changed from typical plate structure to a combination of plate and rod structure with increased connectivity by 202%. Bone strength was reduced by 52%. Bone formation marker, serum osteocalcin of GC-1, was reduced by 71% at 7 months, but recovered with an increase of 45% at 10 month in the GC-2 group. Similar trends were also seen in the femur and tibia. At 10 months, the GC-2 group had microarchitectural and mechanical properties similar to the level of the control sheep.

We have demonstrated in this study that 7 month high-dose GC on bone density and microarchitecture are comparable with those observed in human after long-term GC treatment. Moreover, we have shown that the bone quality with regard to strength and microarchitecture recovers after 3 months further observation without GC. This suggests that a prolonged administration of GC is needed for long-term observation to keep osteopenic bone. The model will be useful in pre-clinical studies.