Effect of ovariectomy, malnutrition and glucocorticoid application on bone properties in sheep: a pilot study.
The demographic changes in the human population continue to lead to an increasing incidence of osteoporosis. The main clinical symptom of osteoporosis is fracture. Fracture fixation in osteoporosis is frequently complicated by failure of fixation. There is a great need for a large-animal model of osteoporosis for controlled studies, which allows the investigation of fracture healing and fracture treatment in weak bone. Eight swiss mountain sheep, 7-9 years old, were divided into four treatment groups of two animals each. Group 1 was ovariectomized and fed a calcium/vitamin D-restricted diet (O+D). Group 2 was ovariectomized and given a daily intramuscular injection of 25 mg methylprednisolone (O+S). Group 3 was ovariectomized, fed a calcium/vitamin D-restricted diet and injected with 25 mg intramuscular methylprednisolone per day (O+D+S). Group 4 was used as an untreated, not sham operated control group. At the beginning of the study and every 2 months for 6 months the bone mineral density (BMD) was determined using quantitative computed tomography (pQCT) at the distal radius. Biopsies were taken after 6 months from vertebral bodies and femoral heads and the bone structure, i.e. trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), bone surface fraction (BS/BV) and bone volume fraction (BV/TV), was determined by micro-CT. In vitro compression testing of the biopsies was performed to determine failure load and stiffness. The control group showed no changes in BMD. The greatest decrease in BMD was seen in group 3 (O+D+S), which had a decline of 58% in cancellous bone and 22% in cortical bone. In the vertebral body biopsies a prominent change in structural parameters was observed (Tb.N, -53%; Tb.Th, -63%, Tb.Sp, +150%). The changes were less pronounced in the femoral head biopsies. In the compression test the vertebral body biopsies of group 3 (O+D+S) had stiffness values 40% lower failure load 70% lower compared with the control group. The most effective method of inducing osteoporosis in sheep was found to be the combined treatment. These results need to be confirmed in a larger number of animals.