Sheep model for fracture treatment in osteoporotic bone: A pilot study about different induction regimens

Objective: Various regimens to induce osteoporosis in sheep were compared to establish a large animal model for further studies of fracture healing and fracture treatment in severe osteoporosis. Design: Prospective, randomized animal study (six months' duration). Participants: Eight sheep (seven to nine years old) were divided into four treatment groups of two animals each. Intervention: Group 1: Ovariectomy (OVX) + calcium/ vitamin D-restricted diet (O + D); Group 2: Ovariectomy + daily injection of steroids (O + S); Group 3: Ovariectomy + daily injection of steroids + calcium/vitamin D-restricted diet (O + D + 3); Group 4: Control, untreated. Main Outcome Measurements: Preoperatively and every 2 months, the bone mineral density (BMD) was determined by quantitative computed tomography (QCT) bilaterally at the distal tibia. Bone structural parameters were determined from iliac crest biopsy specimens using micro-CT. In vitro torsional stiffness of tibia segments was measured. Results: The control group showed a slight increase in BMD with time. The greatest decrease in BMD was seen in Group 3, with a decrease of 55 percent in cancellous bone and 7 percent in cortical bone. In the iliac crest biopsy specimens, trabecular number decreased 19 percent, trabecular thickness decreased 22 percent, and bone volume fraction decrased 37 percent during the 6 months. The torsional strength and stiffness of the tibia showed a difference of approximately 50 percent between Group 3 and the control group. Conclusions: The induction of severe osteoporosis in sheep is best possible by combined treatment with ovariectomy, calcium/vitamin D-restricted diet, and steroids. There is a good relationship between density, structural parameters, and mechanical properties of bone.